Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 296
Filter
1.
Clin Infect Dis ; 75(Supplement_1): S37-S45, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992143

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Immunoglobulin A , Immunoglobulin G , Infant , Infant, Newborn , Lactation , Placenta , Pregnancy , Prospective Studies , SARS-CoV-2 , Vaccination
2.
Front Cell Infect Microbiol ; 12: 873253, 2022.
Article in English | MEDLINE | ID: covidwho-1987468

ABSTRACT

Pregnancy causes physiological and immunological adaptations that allow the mother and fetus to communicate with precision in order to promote a healthy pregnancy. At the same time, these adaptations may make pregnant women more susceptible to infections, resulting in a variety of pregnancy complications; those pathogens may also be vertically transmitted to the fetus, resulting in adverse pregnancy outcomes. Even though the placenta has developed a robust microbial defense to restrict vertical microbial transmission, certain microbial pathogens have evolved mechanisms to avoid the placental barrier and cause congenital diseases. Recent mechanistic studies have begun to uncover the striking role of the maternal microbiota in pregnancy outcomes. In this review, we discuss how microbial pathogens overcome the placental barrier to cause congenital diseases. A better understanding of the placental control of fetal infection should provide new insights into future translational research.


Subject(s)
Placenta , Pregnancy Complications, Infectious , Child , Child Health , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy
3.
BMJ ; 378: e069741, 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-1986354

ABSTRACT

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.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Infant , Lactation , Placenta , Pregnancy , SARS-CoV-2 , Vaccination/adverse effects
5.
Vaccine ; 40(32): 4361-4370, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1977884

ABSTRACT

Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infection (ALRI), including bronchiolitis and pneumonia, in infants and children worldwide. Protection against RSV is primarily antibody mediated and passively acquired RSV neutralizing antibody can protect infants from RSV ALRI. Maternal immunization is an attractive strategy for the prevention of RSV in early infancy when immune responses to active immunization may be suboptimal and most severe RSV disease and death occur. However, several biologic factors have been shown to potentially attenuate or interfere with the transfer of protective naturally acquired antibodies from mother to fetus and could therefore also reduce vaccine effectiveness through impairment of transfer of vaccine-induced antibodies. Many of these factors are prevalent in low- and middle-income countries (LMIC) which experience the greatest burden of RSV-associated mortality; more data are needed to understand these mechanisms in the context of RSV maternal immunization. This review will focus on what is currently known about biologic conditions that may impair RSV antibody transfer, including preterm delivery, low birthweight, maternal HIV infection, placental malaria, and hypergammaglobulinemia (high levels of maternal total IgG). Key data gaps and priority areas for research are highlighted and include improved understanding of the epidemiology of hypergammaglobulinemia and the mechanisms by which it may impair antibody transfer. Key considerations for ensuring optimal vaccine effectiveness in LMICs are also discussed.


Subject(s)
HIV Infections , Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Antibodies, Viral , Biological Factors , Child , Developing Countries , Female , Humans , Hypergammaglobulinemia , Immunization , Infant , Infant, Newborn , Placenta , Policy , Pregnancy , Research , Respiratory Syncytial Virus Infections/prevention & control , Vaccination
6.
Int J Environ Res Public Health ; 19(15)2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1969276

ABSTRACT

The association between maternal COVID-19 infection, placental histomorphology and perinatal outcomes is uncertain. The published studies on how placental structure is affected after SARS-CoV-2 virus in COVID-19-infected pregnant women are lacking. We investigated the effects of maternal SARS-CoV-2 infection on placental histomorphology and pregnancy outcomes. A retrospective cohort study on 47 pregnant women with confirmed SARS-CoV-2 infection, matched with non-infected controls, was conducted. Relevant clinicopathological data and primary birth outcomes were recorded. Histomorphology and SARS-CoV-2 immunohistochemistry analyses of placental tissues were performed. Only 1 of 47 cases showed SARS-CoV-2 immunoreactivity in the syncytiotrophoblasts. Histologically, decidual vasculopathy (n = 22/47, p = 0.004), maternal vascular thrombosis (n = 9/47, p = 0.015) and chronic histiocytic intervillositis (n = 10/47, p = 0.027) were significantly higher in the COVID-19-infected placentas when compared to the control group. Maternal vascular thrombosis was a significant feature in the active COVID-19 group. A significant lower gestational age (p < 0.001)) at delivery and a higher caesarean section rate (p = 0.007) were observed in the active SARS-CoV-2-infected cases, resulting in a significant lower fetal-placental weight ratio (p = 0.022) and poorer Apgar score (p < 0.001). Notably, active (p = 0.027), symptomatic (p = 0.039), severe-critical (p = 0.002) maternal COVID-19 infection and placental inflammation (p = 0.011) were associated with an increased risk of preterm delivery. Altered placental villous maturation and severe-critical maternal COVID-19 infection were associated with an elevated risk of poor Apgar scores at birth (p = 0.018) and maternal mortality (p = 0.023), respectively.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Cesarean Section , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
7.
PLoS One ; 17(7): e0268591, 2022.
Article in English | MEDLINE | ID: covidwho-1968858

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 has been causing the pandemic of coronavirus disease 2019 (COVID-19) that has so far resulted in over 450 million infections and six million deaths. This respiratory virus uses angiotensin-converting enzyme 2 as a receptor to enter host cells and affects various tissues in addition to the lungs. The present study reports that the placental arteries of women who gave birth to live full-term newborns while developing COVID-19 during pregnancy exhibit severe vascular wall thickening and the occlusion of the vascular lumen. A morphometric analysis of the placental arteries stained with hematoxylin and eosin suggests a 2-fold increase in wall thickness and a 5-fold decrease in the lumen area. Placental vascular remodeling was found to occur in all of SARS-CoV-2-positive mothers as defined by RT-PCR. Immunohistochemistry with α-smooth muscle actin and the Kv11.1 channel as well as Masson's trichrome staining showed that such placental vascular remodeling in COVID-19 is associated with smooth muscle proliferation and fibrosis. Placental vascular remodeling may represent a response mechanism to the clinical problems associated with childbirth in COVID-19 patients.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infant, Newborn , Placenta , Pregnancy , Pregnant Women , SARS-CoV-2 , Vascular Remodeling
8.
Nat Commun ; 13(1): 4422, 2022 Jul 30.
Article in English | MEDLINE | ID: covidwho-1967602

ABSTRACT

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Immunoglobulin G , Infant, Newborn , Placenta , Pregnancy , RNA, Messenger , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
9.
Viruses ; 14(6)2022 06 18.
Article in English | MEDLINE | ID: covidwho-1964107

ABSTRACT

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a "barrier" to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms' severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Angiotensin-Converting Enzyme 2 , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , SARS-CoV-2
10.
Ital J Pediatr ; 48(1): 100, 2022 Jun 16.
Article in English | MEDLINE | ID: covidwho-1962868

ABSTRACT

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.


Subject(s)
COVID-19 , Hematologic Diseases , Hyperbilirubinemia, Neonatal , Infant, Newborn, Diseases , Polycythemia , COVID-19/epidemiology , Female , Humans , Hyperbilirubinemia, Neonatal/epidemiology , Hyperbilirubinemia, Neonatal/therapy , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Pandemics , Placenta , Polycythemia/epidemiology , Pregnancy , RNA, Viral , SARS-CoV-2
11.
Placenta ; 126: 209-223, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1937083

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Placenta/metabolism , Pregnancy , SARS-CoV-2 , Trophoblasts/pathology
12.
Vaccine ; 40(27): 3746-3751, 2022 06 15.
Article in English | MEDLINE | ID: covidwho-1926964

ABSTRACT

BACKGROUND: Immunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. METHODS: Paired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction. RESULTS: Annual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2-10.9) vs. 8.4 IU/ml (5.1-13.9; p = 0.004); 18.8 IU/ml (10.9-32.2) vs. 23.6 IU/ml (13.2-42.1; p < 0.001); and 37.1 IU/ml (18.1-75.9) vs. 47.2 IU/ml (24.8-89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018-2019, 8.4 IU/ml (95% CI, 5.1-13.9) vs. 5.4 IU/ml (95% CI, 3.8-7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2-42.1) vs. 20.1 IU/ml (95% CI, 13.4-30.2; p = 0.656), and 47.2 IU/ml (24.8-89.9) vs. 17.3 IU/ml (95% CI, 10.5-28.7; p = 0.021), respectively. DISCUSSION: B. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.


Subject(s)
COVID-19 , Whooping Cough , Antibodies, Bacterial , Bordetella pertussis , British Columbia , COVID-19/epidemiology , COVID-19/prevention & control , Child , Female , Humans , Immunoglobulin G , Infant , Pandemics , Pertussis Toxin , Placenta , Pregnancy , Whooping Cough/epidemiology , Whooping Cough/prevention & control
13.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1923523

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Placenta/pathology , Pregnancy Complications, Infectious/therapy , Adult , COVID-19/diagnosis , Cesarean Section , Female , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Trimester, Second , Treatment Outcome
14.
Placenta ; 126: 125-132, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1914907

ABSTRACT

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibodies, Viral , Female , Humans , Immunoglobulin G , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2 , Trophoblasts/pathology
15.
Placenta ; 124: 62-66, 2022 06 24.
Article in English | MEDLINE | ID: covidwho-1914906

ABSTRACT

INTRODUCTION: COVID-19 has been associated with several adverse pregnancy outcomes, including perinatal loss. Differential effects of COVID-19 in a twin pregnancy may provide unique insights into virus-placental interactions. We present a case of perinatal loss of a female fetus with survival of the male co-twin in a pregnancy complicated by COVID-19 and premature delivery. METHODS: Viral detection methods recommended by the NICHD task force were used to identify SARS-CoV-2 and its viral receptors in the placentas and fetal tissue (Antoun et al., 2020) [1] RESULTS: Compared with the surviving twin, we found a more severe intervillous necrosis and a relatively low detection of ACE2 membranous expression in the syncytiotrophoblasts of the female twin that succumbed. DISCUSSION: The interactions of SARS-CoV-2 and ACE2 at the maternal fetal interface within the placenta may play a significant role in perinatal loss, and the effects of fetal sex and gestational age at time of infection need to be explored further.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Angiotensin-Converting Enzyme 2 , Female , Humans , Infectious Disease Transmission, Vertical , Male , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/pathology , SARS-CoV-2
16.
EBioMedicine ; 81: 104095, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1914309

ABSTRACT

BACKGROUND: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues. METHODS: To test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUCfetus/AUCmother). FINDINGS: Our in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The Cmax and AUClast values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats. INTERPRETATION: While remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy. FUNDING: Ministry of Science and Technology of Taiwan.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Adenosine/analogs & derivatives , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amniotic Fluid , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biotransformation , COVID-19/drug therapy , Female , Fetus/metabolism , Furans/metabolism , Placenta/metabolism , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pyrroles/metabolism , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry/methods
17.
Nat Commun ; 13(1): 3571, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1908170

ABSTRACT

The availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Ad26COVS1 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Immunity , Infant, Newborn , Placenta , Pregnancy , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2 , United States , Vaccination/methods
18.
Front Immunol ; 13: 910138, 2022.
Article in English | MEDLINE | ID: covidwho-1903030

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has turned pregnant women's healthcare into a worldwide public health challenge. Although initial data did not demonstrate pregnancy as a more susceptible period to severe outcomes of acute severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection, there are an increasing number of reports showing that not only pregnant women might be at significantly higher risk than non-pregnant women by COVID-19 but also the fetus. These findings may be related to adaptive changes that occur during pregnancy, such as the reduction in the residual respiratory capacity, the decrease in viral immune responses, and the increased risk for thromboembolic events. Additionally, despite the SARS-CoV-2 vertical transmission evidence being uncommon, maternal illness severity might reflect serious perinatal and neonatal outcomes. Thus, protecting the maternal-fetal dyad against COVID-19 is critical. Even though pregnant women initially were excluded from vaccine trials, several studies have provided safety and efficacy of the overall vaccine COVID-19 platforms. Vaccination during pregnancy becomes a priority and can generate benefits for both the mother and newborn: maternal neutralizing antibodies are transmitted through the placenta and breastfeeding. Moreover, regarding passive immunization, human milk contains other bioactive molecules and cells able to modulate the newborn's immune response, which can be amplified after the vaccine. Nonetheless, many issues remain to be elucidated, considering the magnitude of the protective immunity transferred, the duration of the induced immunity, and the optimal interval for pregnant immunization. In this review, we assessed these unmet topics supported by literature evidence regarding the vaccine's immunogenicity, pregnancy immune heterogeneity, and the unique human milk antiviral features.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Vaccines , Breast Feeding , COVID-19/prevention & control , Female , Humans , Infant, Newborn , Pandemics/prevention & control , Placenta , Pregnancy , Pregnancy Complications, Infectious/prevention & control , SARS-CoV-2
19.
J Matern Fetal Neonatal Med ; 35(15): 3016-3019, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1900912

ABSTRACT

SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus-receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/complications , Female , Humans , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Renin-Angiotensin System/physiology , SARS-CoV-2
20.
J Matern Fetal Neonatal Med ; 35(15): 2965-2968, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1900901

ABSTRACT

BACKGROUND: COVID-19 has rapidly spread worldwide, with severe complications affecting particularly elderly and compromised subjects. Less information about COVID-19 in pregnancy has been reported so far in the literature. METHODS: Case series on pregnancies complicated by COVID-19. All cases were diagnosed at Bolognini Hospital, Seriate, Italy. These cases are presented to clarify the features of COVID-19 occurring in pregnancy. RESULTS: Four women had symptoms of COVID-19 during pregnancy or immediately after delivery. All cases were confirmed by oropharyngeal swab. All patients presented with fever and low saturation levels at the diagnosis. One case was transferred after diagnosis to a tertiary referral center and delivered the day after for worsening clinical conditions. In the other three cases, bilateral pneumonia was documented at the admission. Antithrombotic therapy was used in most cases. No cases of the infected neonate was reported. At 2 month follow-up, all patients were alive, three were asymptomatic while one presented neurological complication. One more case was described because suspicious for COVID-19, however, it was not confirmed by oropharyngeal swab. CONCLUSIONS: In pregnant women, the peripheral nervous system could be affected. No case of trans-placental passage was reported. The swab could be helpful in diagnosis. The antithrombotic therapy could play a role in the positive course of COVID-19 also in pregnant women.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Aged , COVID-19/complications , COVID-19/epidemiology , Disease Outbreaks , Female , Fibrinolytic Agents , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome/epidemiology , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL