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1.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758757

RESUMO

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.


Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Placenta/patologia , Complicações Infecciosas na Gravidez/terapia , Adulto , COVID-19/diagnóstico , Cesárea , Feminino , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Segundo Trimestre da Gravidez , Resultado do Tratamento
2.
Diagn Pathol ; 16(1): 88, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602071

RESUMO

INTRODUCTION: COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. CASE REPORTS: All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. CONCLUSIONS: In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases.


Assuntos
COVID-19/diagnóstico por imagem , Transmissão Vertical de Doenças Infecciosas , Pandemias , Complicações Infecciosas na Gravidez , SARS-CoV-2/fisiologia , Adulto , COVID-19/epidemiologia , COVID-19/patologia , COVID-19/virologia , Feminino , Humanos , Recém-Nascido , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta/virologia , Gravidez , Resultado da Gravidez , Tomografia Computadorizada por Raios X , Trofoblastos/patologia , Trofoblastos/virologia
3.
Front Immunol ; 12: 743022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603330

RESUMO

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.


Assuntos
COVID-19/patologia , Placenta/patologia , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Aborto Espontâneo/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Feminino , Retardo do Crescimento Fetal/virologia , Humanos , Troca Materno-Fetal/fisiologia , Gravidez , SARS-CoV-2/patogenicidade , Serina Endopeptidases/metabolismo , Natimorto
4.
Placenta ; 115: 37-44, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34537470

RESUMO

INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. DISCUSSION: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.


Assuntos
COVID-19 , Doenças Placentárias/etiologia , Complicações Infecciosas na Gravidez , Estresse Psicológico/complicações , Adolescente , Adulto , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/psicologia , Canadá/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Masculino , Relações Materno-Fetais/psicologia , Pessoa de Meia-Idade , Pandemias , Placenta/patologia , Placenta/virologia , Doenças Placentárias/epidemiologia , Doenças Placentárias/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/psicologia , Resultado da Gravidez/epidemiologia , Resultado da Gravidez/psicologia , Angústia Psicológica , SARS-CoV-2/fisiologia , Estresse Psicológico/etiologia , Estresse Psicológico/patologia , Reino Unido/epidemiologia , Adulto Jovem
6.
Viruses ; 13(9)2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34578466

RESUMO

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/fisiologia , Adulto , Biópsia , COVID-19/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Transmissão Vertical de Doenças Infecciosas , Placenta/patologia , Placenta/virologia , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Resultado da Gravidez , Estudos Retrospectivos , Adulto Jovem
7.
PLoS Pathog ; 17(8): e1009860, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34432853

RESUMO

In 2019, >90% of new HIV infections in infants globally occurred vertically. Studies suggest intrauterine transmission most often occurs in the third trimester; however, there are no mechanistic studies to support these observations. We therefore obtained early/mid-gestation and term placentae from 20 HIV/Hepatitis B/CMV negative women. Isolated primary placental macrophages (Hofbauer cells [HCs]) were exposed to HIV-1BaL and/or interferon (IFN)-α, IFN-ß, IFN-λ1, and RIG-I-like receptor (RLR) agonists. qRT-PCR, FACS, ELISA, Luminex, and Western blot analyses determined expression of activation markers, co-receptors, viral antigen, cytokines, antiviral genes, and host proteins. Early gestation HCs express higher levels of CCR5 and exhibit a more activated phenotype. Despite downregulation of CCR5, term HCs were more susceptible to HIV replication. Early gestation HCs displayed a more activated phenotype than term HCs and HIV exposure lead to the further up-regulation of T-cell co-stimulatory and MHC molecules. Limited HIV replication in early/mid gestation HCs was associated with increased secretion of anti-inflammatory cytokines, chemokines, and a more robust antiviral immune response. In contrast, term HCs were more susceptible to HIV replication, associated with dampening of IFN-induced STAT1 and STAT2 protein activation. Treatment of early/mid gestation and term HCs, with type I IFNs or RLR agonists reduced HIV replication, underscoring the importance of IFN and RLR signaling in inducing an antiviral state. Viral recognition and antiviral immunity in early gestation HCs may prevent in utero HIV infection, whereas diminished antiviral responses at term can facilitate transmission. Defining mechanisms and specific timing of vertical transmission are critical for the development of specific vaccines and antiviral therapeutics to prevent new HIV infections in children globally.


Assuntos
Antivirais/imunologia , Infecções por HIV/prevenção & controle , HIV-1/fisiologia , Imunidade Inata/imunologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Placenta/imunologia , Replicação Viral , Adolescente , Feminino , Idade Gestacional , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Macrófagos/imunologia , Macrófagos/virologia , Placenta/virologia , Gravidez
8.
Ann Clin Lab Sci ; 51(4): 570-572, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452898

RESUMO

COVID-19 has affected patients of all ages and demographics, not excluding pregnant women. The effects of COVID-19 on pregnant women are still largely unknown. Several adverse perinatal outcomes have been reported in COVID-19-positive pregnant women, including pre-eclampsia, miscarriage, pre-term labor, and stillbirth. Histopathological examination of COVID-19 placentas can contribute significant data regarding maternal and fetal health and can elucidate more findings in this novel disease. A 23-year-old female with morbid obesity and scant antenatal care presented to the emergency department complaining of shortness of breath and fever; she was found to be positive for COVID-19. Grossly, her placenta showed no abnormalities. Histological examination of her placenta showed chronic lymphoplasmacytic deciduitis, villous fibrosis, loss of capillarization, extravasation of erythrocytes, chorangiosis, and thrombosis of upstream stem vessels, including large fetal vessels on the chorionic plate. These changes were deemed to be consistent with fetal thrombotic vasculopathy (FTV). In conclusion, this case of FTV in the placenta of a patient with COVID-19 is a significant finding, as it can be critical to clinicians in the management of prenatal care for expecting mothers during this pandemic.This case was presented at the annual meeting of the Association of Clinical Scientists (ACS) on May 13, 2021.


Assuntos
COVID-19/complicações , Doenças Fetais/patologia , Feto/patologia , Doenças Placentárias/patologia , Placenta/patologia , SARS-CoV-2/isolamento & purificação , Trombose/patologia , Adulto , COVID-19/transmissão , COVID-19/virologia , Feminino , Doenças Fetais/virologia , Feto/virologia , Humanos , Placenta/virologia , Doenças Placentárias/virologia , Gravidez , Prognóstico , Trombose/virologia , Adulto Jovem
9.
Clin Sci (Lond) ; 135(15): 1805-1824, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34338772

RESUMO

In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto-maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Placenta/virologia , Complicações Infecciosas na Gravidez/metabolismo , Receptores de Coronavírus/metabolismo , SARS-CoV-2/patogenicidade , Biomarcadores/metabolismo , COVID-19/transmissão , COVID-19/virologia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/virologia , Fatores de Risco , Internalização do Vírus
10.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166244, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34411716

RESUMO

The placenta provides a significant physical and physiological barrier to prevent fetal infection during pregnancy. Nevertheless, it is at times breached by pathogens and leads to vertical transmission of infection from mother to fetus. This review will focus specifically on the Zika flavivirus, the HIV retrovirus and the emerging SARS-CoV2 coronavirus, which have affected pregnant women and their offspring in recent epidemics. In particular, we will address how viral infections affect the immune response at the maternal-fetal interface and how the placental barrier is physically breached and discuss the consequences of infection on various aspects of placental function to support fetal growth and development. Improved understanding of how the placenta responds to viral infections will lay the foundation for developing therapeutics to these and emergent viruses, to minimise the harms of infection to the offspring.


Assuntos
Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Viroses/fisiopatologia , COVID-19/metabolismo , Feminino , Feto/virologia , Infecções por HIV/metabolismo , HIV-1/patogenicidade , Humanos , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , SARS-CoV-2/patogenicidade , Zika virus/patogenicidade , Infecção por Zika virus/metabolismo
11.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166248, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461257

RESUMO

The COVID-19 pandemic has infected nearly 178 million people and claimed the lives of over 3.8 million in less than 15 months. This has prompted a flurry of research studies into the mechanisms and effects of SARS-CoV-2 viral infection in humans. However, studies examining the effects of COVID-19 in pregnant women, their placentae and their babies remain limited. Furthermore, reports of safety and efficacy of vaccines for SARS-CoV-2 in pregnancy are limited. This review concisely summarises the case studies and research on COVID-19 in pregnancy, to date. It also reviews the mechanism of infection with SARS-CoV-2, and its reliance and effects upon the renin-angiotensin-aldosterone system. Overall, the data suggest that infection during pregnancy can be dangerous at any time, but this risk to both the mother and fetus, as well as placental damage, increases during the third trimester. The possibility of vertical transmission, which is explored in this review, remains contentious. However, maternal infection with SARS-CoV-2 can increase risk of miscarriage, preterm birth and stillbirth, which is likely due to damage to the placenta.


Assuntos
COVID-19/metabolismo , Feto/imunologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Feto/virologia , Humanos , Recém-Nascido , Pandemias , Placenta/metabolismo , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2/isolamento & purificação
12.
Viruses ; 13(8)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34452534

RESUMO

BACKGROUND: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. METHODS: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. RESULTS: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0.007) but not with the severity of maternal COVID-19 disease. CONCLUSION: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease.


Assuntos
COVID-19/patologia , Doenças Placentárias/patologia , Placenta/patologia , Complicações Infecciosas na Gravidez/patologia , Adulto , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Sofrimento Fetal/fisiopatologia , Humanos , Estudos Longitudinais , Placenta/fisiopatologia , Placenta/virologia , Doenças Placentárias/fisiopatologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Trofoblastos/patologia
13.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34410903

RESUMO

An infectious agent's pathogenic and transmission potential is heavily influenced by early events during the asymptomatic or subclinical phase of disease. During this phase, the presence of infectious agent may be relatively low. An important example of this is Zika virus (ZIKV), which can cross the placenta and infect the foetus, even in mothers with subclinical infections. These subclinical infections represent roughly 80 % of all human infections. Initial ZIKV pathogenesis studies were performed in type I interferon receptor (IFNAR) knockout mice. Blunting the interferon response resulted in robust infectivity, and increased the utility of mice to model ZIKV infections. However, due to the removal of the interferon response, the use of these models impedes full characterization of immune responses to ZIKV-related pathologies. Moreover, IFNAR-deficient models represent severe disease whereas less is known regarding subclinical infections. Investigation of the anti-viral immune response elicited at the maternal-foetal interface is critical to fully understand mechanisms involved in foetal infection, foetal development, and disease processes recognized to occur during subclinical maternal infections. Thus, immunocompetent experimental models that recapitulate natural infections are needed. We have established subclinical intravaginal ZIKV infections in mice and guinea pigs. We found that these infections resulted in: the presence of both ZIKV RNA transcripts and infectious virus in maternal and placental tissues, establishment of foetal infections and ZIKV-mediated CXCL10 expression. These models will aid in discerning the mechanisms of subclinical ZIKV mother-to-offspring transmission, and by extension can be used to investigate other maternal infections that impact foetal development.


Assuntos
Feto , Placenta , Complicações Infecciosas na Gravidez , Infecção por Zika virus/virologia , Zika virus , Animais , Chlorocebus aethiops , Feminino , Feto/imunologia , Feto/virologia , Cobaias , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placenta/imunologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Células Vero , Zika virus/imunologia , Zika virus/patogenicidade
14.
Arch Pathol Lab Med ; 145(11): 1341-1349, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34338723

RESUMO

CONTEXT.­: Case reports and rare case series have demonstrated variable placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In rare small studies demonstrating infection of the placental parenchyma, histologic manifestations have included variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and syncytiotrophoblast necrosis. OBJECTIVE.­: To characterize the placental pathologic features of SARS-CoV-2-infected placentas, irrespective of fetal-maternal transmission, and to examine the frequency of C4d activation in such cases. DESIGN.­: A retrospective study of 7 placentas from mothers with active SARS-CoV-2 infection and placental infection as demonstrated by RNA in situ hybridization was conducted. RESULTS.­: There were 6 placentas from live-born neonates (5 singletons, 1 nonfused diamniotic-dichorionic twin placenta), and 1 was from a stillbirth. A total of 5 of the 8 neonates (including the stillbirth) tested negative for SARS-CoV-2, and all were negative for neonatal infection. The remaining 3 neonates were well at time of discharge. All placentas were positive for SARS-CoV-2 infection by RNA in situ hybridization and demonstrated variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. Three cases demonstrated features of fetal vascular malperfusion. CD68 highlighted intervillous histiocytes. C4d expression was present along the villous borders in 6 of 7 cases. CONCLUSIONS.­: SARS-CoV-2 placentitis is defined by the triad of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. The features may occur in cases without confirmed transplacental transmission. The damage caused by SARS-CoV-2 placentitis is likely mediated by complement activation.


Assuntos
COVID-19/diagnóstico , Doenças Placentárias/diagnóstico , Placenta/patologia , Placenta/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Biomarcadores/metabolismo , Linfócitos T CD4-Positivos/metabolismo , COVID-19/imunologia , COVID-19/patologia , COVID-19/transmissão , Teste para COVID-19 , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Ativação Linfocitária , Masculino , Doenças Placentárias/imunologia , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Natimorto
15.
Artigo em Inglês | MEDLINE | ID: mdl-34282805

RESUMO

AIMS: Coronavirus disease 2019 is responsible for a worldwide increase in morbidity and mortality. The relationship of this infection to mother-to-child vertical transmission has not been elucidated yet. However, recent reports indicate a foetal death rate of up to 3%. METHODS: We report a case of sudden pre-term foetal demise in a woman positive for SARS-CoV-2 but asymptomatic, with physiological course of pregnancy. RESULTS: One of the possible explanations of sudden foetal death may be acute placental insufficiency caused by a SARS-CoV-2 placental infection or the development of foetal inflammatory response syndrome (FIRS). CONCLUSION: Considering the potential risk of foetal demise, questions remain regarding foetal monitoring and the timing of labour and delivery in the second and third trimesters, particularly in asymptomatic or mild maternal SARS-CoV-2 infection. A relevant multidisciplinary team must also be aware of these risks associated with possibly fatal consequences.


Assuntos
COVID-19/virologia , Morte Fetal , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2/isolamento & purificação , Adulto , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Gravidez
16.
Biochim Biophys Acta Mol Basis Dis ; 1867(10): 166206, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197912

RESUMO

An estimated 1.3 million pregnant women were living with HIV in 2018. HIV infection is associated with adverse pregnancy outcomes and all HIV-positive pregnant women, regardless of their clinical stage, should receive a combination of antiretroviral drugs to suppress maternal viral load and prevent vertical fetal infection. Although antiretroviral treatment in pregnant women has undoubtedly minimized mother-to-child transmission of HIV, several uncertainties remain. For example, while pregnancy is accompanied by changes in pharmacokinetic parameters, relevant data from clinical studies are lacking. Similarly, long-term adverse effects of exposure to antiretrovirals on fetuses have not been studied in detail. Here, we review current knowledge on HIV effects on the placenta and developing fetus, recommended antiretroviral regimens, and pharmacokinetic considerations with particular focus on placental transport. We also discuss recent advances in antiretroviral research and potential effects of antiretroviral treatment on placental/fetal development and programming.


Assuntos
Antirretrovirais/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Animais , Feminino , Humanos , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia
18.
Placenta ; 111: 91-96, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34217121

RESUMO

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mainly transmitted by droplets and close contact, has caused a pandemic worldwide as of March 2020. According to the current case reports and cohort studies, the symptoms of pregnant women infected with SARS-CoV-2 were similar to normal adults and may cause a series of adverse consequences of pregnancy (placental abruption, fetal distress, epilepsy during pregnancy, etc.). However, whether SARS-CoV-2 can be transmitted to the fetus through the placental barrier is still a focus of debate. METHODS: In this study, in order to find out whether SARS-CoV-2 can infect fetus through the placental barrier, we performed qualitative detection of virus structural protein (spike protein and nucleoprotein) and targeted receptor protein Angiotensin Converting Enzyme 2 (ACE2), Basigin (CD147) and molecular chaperone GRP78 expression on the placental tissue of seven pregnant women diagnosed with COVID-19 through immunohistochemistry. Amniotic fluid, neonatal throat, anal swab and breastmilk samples were collected immediately in the operating room or delivery room for verification after delivery, which were all tested for SARS-CoV-2 by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS/DISCUSSION: The result showed that CD147 was expressed on the basal side of the chorionic trophoblast cell membrane and ACE2 was expressed on the maternal side, while GRP78 was strongly expressed in the cell membrane and cytoplasm. The RT-PCR results of Amniotic fluid, neonatal throat, anal swab and breastmilk samples were all negative. On the basis of these findings, we speculated that it may be due to the placental barrier between mother and baby, for example, villous matrix and interstitial blood vessels have low expression of virus-related receptors (ACE2, CD147, GRP78), the probability of vertical transmission of SARS-CoV-2 through the placenta is low.


Assuntos
COVID-19/transmissão , Transmissão Vertical de Doenças Infecciosas , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , SARS-CoV-2 , Adulto , Líquido Amniótico/virologia , Enzima de Conversão de Angiotensina 2/análise , Basigina/análise , Teste para COVID-19 , China , Feminino , Doenças Fetais/virologia , Proteínas de Choque Térmico/análise , Humanos , Recém-Nascido , Nucleoproteínas/análise , Placenta/química , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Glicoproteína da Espícula de Coronavírus/análise
19.
Placenta ; 112: 97-104, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34329973

RESUMO

INTRODUCTION: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. METHOD: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. RESULTS: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DISCUSSION: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.


Assuntos
COVID-19/complicações , Doenças Placentárias/etiologia , Nascimento Prematuro/etiologia , Natimorto , Adulto , COVID-19/diagnóstico , COVID-19/patologia , Feminino , Morte Fetal/etiologia , França , Humanos , Recém-Nascido , Masculino , Morte Perinatal/etiologia , Placenta/patologia , Placenta/virologia , Doenças Placentárias/diagnóstico , Doenças Placentárias/patologia , Doenças Placentárias/virologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Nascimento Prematuro/patologia , Nascimento Prematuro/virologia , SARS-CoV-2/fisiologia , Trofoblastos/patologia , Trofoblastos/virologia
20.
Cell Prolif ; 54(9): e13091, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291856

RESUMO

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.


Assuntos
Citocinas/análise , Placenta/virologia , RNA Viral/isolamento & purificação , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Proteínas Virais/isolamento & purificação , Adulto , Líquido Amniótico/química , COVID-19/patologia , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Macrófagos/imunologia , Técnicas de Amplificação de Ácido Nucleico , Placenta/imunologia , Gravidez , RNA Viral/sangue , RNA Viral/genética , SARS-CoV-2/isolamento & purificação , Proteínas Virais/sangue
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