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1.
J Med Case Rep ; 15(1): 104, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648584

RESUMO

BACKGROUND: Pregnancy seems to increase the risk of thrombotic thrombocytopenic purpura (TTP) relapses and make the TTP more severe in any of the pregnancy trimesters, or even during the postpartum period. CASE PRESENTATION: This study highlights details of treating a COVID-19 pregnant patient who survived. This 21-year addicted White woman was admitted at her 29th week and delivered a stillbirth. She was transferred to another hospital after showing signs of TTP, which was caused by a viral infection. CONCLUSION: This viral infection caused fever and dyspnea, and the patient was tested positive for COVID-19 infection. A chest computed tomography scan showed diffuse multiple bilateral consolidations and interlobar septal thickening. She stayed at the Intensive Care Unit for 20 days and treated with plasmapheresis. As far as we know, this is the first report of a TTP pregnant patient with COVID-19 infection.


Assuntos
/diagnóstico , Plasmaferese , Complicações Hematológicas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Natimorto , Lesão Renal Aguda/terapia , Transtornos Relacionados ao Uso de Anfetaminas , Antivirais/uso terapêutico , Combinação de Medicamentos , Transfusão de Eritrócitos , Feminino , Hemoglobinas/metabolismo , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , L-Lactato Desidrogenase/metabolismo , Lopinavir/uso terapêutico , Metanfetamina , Gravidez , Complicações Hematológicas na Gravidez/metabolismo , Complicações Hematológicas na Gravidez/terapia , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/terapia , Púrpura Trombocitopênica Trombótica/metabolismo , Púrpura Trombocitopênica Trombótica/terapia , Diálise Renal , Ritonavir/uso terapêutico , Tomografia Computadorizada por Raios X , Adulto Jovem
2.
Clin Ther ; 43(2): 308-318, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33541739

RESUMO

PURPOSE: The majority of pregnancies affected by maternal coronavirus disease 2019 (COVID-19) do not result in fetal transmission. However, several studies have identified parenchymal changes in their placental tissues, suggesting a placental response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the maternal-fetal interface. Although many COVID-19 placental studies have focused on the expression of the canonical SARS-CoV-2 entry proteins angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2, further characterization of subcellular molecules involved in viral trafficking have not yet been investigated in these tissues. Of interest are Rab proteins, a family of small GTPase proteins that direct intracellular transport between different endocytic organelles. Rab5 and Rab7 in particular have previously been implicated in HIV and cytomegalovirus invasion of placental trophoblast cells in vitro; the localization of these molecules has not been fully characterized within the human maternal-fetal interface, however, or within placental tissues from SARS-CoV-2-infected pregnancies. METHODS: Using fluorescent immunohistochemistry, Rab5 and Rab7 placental localization and comparative fluorescence intensity were explored in a cohort of placental tissues from pregnancies affected by maternal COVID-19 disease (COVID, n = 15) compared with contemporary control subjects (Control, n = 10). Fluorescence intensity was quantified by using corrected total cell fluorescence values. FINDINGS: Within placental villi, Rab5 was consistently localized in syncytiotrophoblast and cytotrophoblast cells. Rab5 had significantly higher mean (SEM) fluorescence intensity in the COVID cohort (Control, 1.96 [0.16]; COVID, 2.62 [0.09]; P = 0.0014). In contrast, although Rab7 was also localized within placental villous syncytiotrophoblast and cytotrophoblast cells, mean (SEM) Rab7 fluorescence intensity was significantly downregulated in COVID vs Control placentas (Control, 35.9 [4.1]; COVID, 20.1 [0.52]; P = 0.0001). IMPLICATIONS: This differential expression of Rab5 and Rab7 suggests that placental endocytic pathways may be altered at the maternal-fetal interface in pregnancies affected by maternal SARS-CoV-2 infection. As key molecules governing intracellular vesicle transport, including viral trafficking, Rab GTPase proteins may be of interest for ongoing studies examining placental responses to COVID-19 in pregnancy.


Assuntos
/metabolismo , Placenta/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Trofoblastos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo , Feminino , Humanos , Gravidez , Complicações Infecciosas na Gravidez/virologia
3.
Viruses ; 13(1)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430059

RESUMO

BACKGROUND: Zika virus (ZIKV) infection during pregnancy usually shows only mild symptoms and is frequently subclinical. However, it can be vertically transmitted to the fetus, causing microcephaly and other congenital defects. During pregnancy, the immune environment modifications can alter the response to viruses in general and ZIKV in particular. OBJECTIVE: To describe the role of pregnancy in the systemic pro- and anti-inflammatory response during symptomatic ZIKV infection. MATERIALS AND METHODS: A multiplex assay was used to measure 25 cytokines, chemokines, and receptors in 110 serum samples from pregnant and nonpregnant women with and without ZIKV infection with and without symptoms. Samples were collected through an epidemiological surveillance system. RESULTS: Samples from pregnant women with ZIKV infection showed a higher viral load but had similar profiles of inflammatory markers as compared with nonpregnant infected women, except for CXCL10 that was higher in infected pregnant women. Notably, the presence of ZIKV in pregnancy favored a regulatory profile by significantly increasing anti-inflammatory cytokines such as interleukin (IL)-10, receptors IL-1RA, and IL-2R, but only those pro-inflammatory cytokines such as IL-6, interferon (IFN)-α, IFN-γ and IL-17 that are essential for the antiviral response. Interestingly, there were no differences between symptomatic and weakly symptomatic ZIKV-infected groups. CONCLUSION: Our results revealed a systemic anti-inflammatory cytokine and chemokine profile that could participate in the control of the virus. The anti-inflammatory response in pregnant women infected with ZIKA was characterized by high CXCL10, a cytokine that has been correlated with congenital malformations.


Assuntos
Quimiocina CXCL10/metabolismo , Citocinas/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/virologia , Carga Viral , Infecção por Zika virus/metabolismo , Infecção por Zika virus/virologia , Zika virus/fisiologia , Adulto , Biomarcadores , Feminino , Humanos , Imunomodulação , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Trimestres da Gravidez , Adulto Jovem , Infecção por Zika virus/imunologia
4.
Mod Pathol ; 33(11): 2092-2103, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32741970

RESUMO

Congenital infection of SARS-CoV-2 appears to be exceptionally rare despite many cases of COVID-19 during pregnancy. Robust proof of placental infection requires demonstration of viral localization within placental tissue. Only two of the few cases of possible vertical transmission have demonstrated placental infection. None have shown placental expression of the ACE2 or TMPRSS2 protein, both required for viral infection. We examined 19 COVID-19 exposed placentas for histopathologic findings, and for expression of ACE2, and TMPRSS2 by immunohistochemistry. Direct placental SARS-CoV-2 expression was studied by two methods-nucleocapsid protein expression by immunohistochemistry, and RNA expression by in situ hybridization. ACE2 membranous expression in the syncytiotrophoblast (ST) of the chorionic villi is predominantly in a polarized pattern with expression highest on the stromal side of the ST. In addition, cytotrophoblast and extravillous trophoblast express ACE2. No ACE2 expression was detected in villous stroma, Hofbauer cells, or endothelial cells. TMPRSS2 expression was only present weakly in the villous endothelium and rarely in the ST. In 2 of 19 cases, SARS-CoV-2 RNA was present in the placenta focally in the ST and cytotrophoblast. There was no characteristic histopathology present in our cases including the two placental infections. We found that the placenta is capable of being infected but that this event is rare. We propose one explanation could be the polarized expression of ACE2 away from the maternal blood and pronounced paucity of TMPRSS2 expression in trophoblast.


Assuntos
Infecções por Coronavirus/virologia , Placenta/patologia , Placenta/virologia , Pneumonia Viral/virologia , Complicações Infecciosas na Gravidez/virologia , Adulto , Betacoronavirus , Infecções por Coronavirus/patologia , Feminino , Humanos , Pandemias , Peptidil Dipeptidase A/biossíntese , Placenta/metabolismo , Pneumonia Viral/patologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , RNA Viral/análise , Serina Endopeptidases/biossíntese
5.
BMC Pregnancy Childbirth ; 20(1): 481, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838744

RESUMO

BACKGROUND: The world's understanding of COVID-19 continues to evolve as the scientific community discovers unique presentations of this disease. This case report depicts an unexpected intraoperative coagulopathy during a cesarean section in an otherwise asymptomatic patient who was later found to have COVID-19. This case suggests that there may be a higher risk for intrapartum bleeding in the pregnant, largely asymptomatic COVID-positive patient with more abnormal COVID laboratory values. CASE: The case patient displayed D-Dimer elevations beyond what is typically observed among this hospital's COVID-positive peripartum population and displayed significantly more oozing than expected intraoperatively, despite normal prothrombin time, international normalized ratio, fibrinogen, and platelets. CONCLUSION: There is little published evidence on the association between D-Dimer and coagulopathy among the pregnant population infected with SARS-CoV-2. This case report contributes to the growing body of evidence on the effects of COVID-19 in pregnancy. A clinical picture concerning for intraoperative coagulopathy may be associated with SARS-CoV-2 infection during cesarean sections, and abnormal COVID laboratory tests, particularly D-Dimer, may help identify the patients in which this presentation occurs.


Assuntos
Transtornos da Coagulação Sanguínea/sangue , Perda Sanguínea Cirúrgica , Apresentação Pélvica/cirurgia , Cesárea , Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Complicações Hematológicas na Gravidez/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Antifibrinolíticos/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/metabolismo , Proteína C-Reativa/metabolismo , Cauterização , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinogênio/metabolismo , Hemostasia Cirúrgica , Humanos , Coeficiente Internacional Normatizado , Metilergonovina/uso terapêutico , Oligo-Hidrâmnio , Ocitócicos/uso terapêutico , Ocitocina/uso terapêutico , Pandemias , Contagem de Plaquetas , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Gravidez , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Hematológicas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/metabolismo , Tempo de Protrombina , Ácido Tranexâmico/uso terapêutico , Inércia Uterina/tratamento farmacológico
6.
Nat Commun ; 11(1): 2967, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32528049

RESUMO

The recent outbreak of Zika virus (ZIKV) was associated with birth defects and pregnancy loss when maternal infection occurs in early pregnancy, but specific mechanisms driving placental insufficiency and subsequent ZIKV-mediated pathogenesis remain unclear. Here we show, using large scale metabolomics, that ZIKV infection reprograms placental lipidome by impairing the lipogenesis pathways. ZIKV-induced metabolic alterations provide building blocks for lipid droplet biogenesis and intracellular membrane rearrangements to support viral replication. Furthermore, lipidome reprogramming by ZIKV is paralleled by the mitochondrial dysfunction and inflammatory immune imbalance, which contribute to placental damage. In addition, we demonstrate the efficacy of a commercially available inhibitor in limiting ZIKV infection, provides a proof-of-concept for blocking congenital infection by targeting metabolic pathways. Collectively, our study provides mechanistic insights on how ZIKV targets essential hubs of the lipid metabolism that may lead to placental dysfunction and loss of barrier function.


Assuntos
Placenta/virologia , Infecção por Zika virus/imunologia , Infecção por Zika virus/metabolismo , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa , Lipidômica/métodos , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/metabolismo , Zika virus/imunologia , Zika virus/patogenicidade
7.
BJOG ; 127(11): 1374-1380, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32479682

RESUMO

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.


Assuntos
Infecções por Coronavirus/fisiopatologia , Síndrome HELLP/fisiopatologia , Fator de Crescimento Placentário/metabolismo , Pneumonia Viral/fisiopatologia , Pré-Eclâmpsia/fisiopatologia , Complicações Infecciosas na Gravidez/fisiopatologia , Artéria Uterina/diagnóstico por imagem , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Betacoronavirus , Pressão Sanguínea , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Feminino , Síndrome HELLP/etiologia , Síndrome HELLP/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Proteinúria/etiologia , Proteinúria/fisiopatologia , Fluxo Pulsátil , Índice de Gravidade de Doença , Centros de Atenção Terciária , Trombocitopenia/etiologia , Trombocitopenia/fisiopatologia
8.
Cell Mol Biol (Noisy-le-grand) ; 66(3): 221-229, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32538775

RESUMO

It can be misleading to think that the new severe acute respiratory syndrome coronavirus (SARS-CoV2) which has a very strong mutation and adaptation capabilities, uses only the angiotensin-converting enzyme II (ACE2) pathway to reach target cells. Despite all the precautions taken, the pandemic attack continues and the rapid increase in the number of deaths suggest that this virus has entered the cell through different pathways and caused damage through different mechanisms. The main reason why the ACE2 pathway comes to the fore in all scientific studies is that this receptor is located at the entry point of basic mechanisms that provide alveolo-capillary homeostasis. SARS-CoV-2 has to use nuclear factor-κB (NF-kB), caveloae, clathrin, lipoxin, serine protease and proteasome pathways in addition to ACE2 to enter the target cell and initiate damage. For this reason, while new drug development studies are continuing, in order to be beneficial to patients in their acute period, it is imperative that we are able to come up with drugs that activate or inhibit these pathways and are currently in clinical use. It is also critical that we adopt these new pathways to the treatment of pregnant women affected by SARS-CoV-2, based on the scientific data we use to treat the general population.


Assuntos
Betacoronavirus/metabolismo , Caveolina 1/metabolismo , Infecções por Coronavirus/metabolismo , Lipoxinas/metabolismo , NF-kappa B/metabolismo , Pneumonia Viral/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Sítios de Ligação , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Descoberta de Drogas/métodos , Reposicionamento de Medicamentos/métodos , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , NF-kappa B/antagonistas & inibidores , Uso Off-Label , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Inibidores de Proteassoma/uso terapêutico , Serina Endopeptidases/metabolismo , Inibidores de Serino Proteinase/uso terapêutico , Internalização do Vírus
10.
PLoS Pathog ; 16(5): e1008521, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32392268

RESUMO

Zika virus (ZIKV) infection may lead to congenital microcephaly and pregnancy loss in pregnant women. In the context of pregnancy, folic acid (FA) supplementation may reduce the risk of abnormal pregnancy outcomes. Intriguingly, FA may have a beneficial effect on the adverse pregnancy outcomes associated with ZIKV infection. Here, we show that FA inhibits ZIKV replication in human umbilical vein endothelial cells (HUVECs) and a cell culture model of blood-placental barrier (BPB). The inhibitory effect of FA against ZIKV infection is associated with FRα-AMPK signaling. Furthermore, treatment with FA reduces pathological features in the placenta, number of fetal resorptions, and stillbirths in two mouse models of in utero ZIKV transmission. Mice with FA treatment showed lower viral burden and better prognostic profiles in the placenta including reduced inflammatory response, and enhanced integrity of BPB. Overall, our findings suggest the preventive role of FA supplementation in ZIKV-associated abnormal pregnancy and warrant nutritional surveillance to evaluate maternal FA status in areas with active ZIKV transmission.


Assuntos
Ácido Fólico/farmacologia , Placenta , Complicações Infecciosas na Gravidez , Infecção por Zika virus/prevenção & controle , Zika virus/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Microcefalia/metabolismo , Microcefalia/patologia , Microcefalia/prevenção & controle , Microcefalia/virologia , Placenta/metabolismo , Placenta/patologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/prevenção & controle , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia
11.
Diabetes Metab Syndr ; 14(4): 519-520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388332

RESUMO

BACKGROUND AND AIMS: Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. METHODS: We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. RESULTS: SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. CONCLUSIONS: Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.


Assuntos
Corticosteroides/farmacologia , Infecções por Coronavirus/complicações , Diabetes Mellitus/fisiopatologia , Hiperglicemia/patologia , Hipoglicemia/patologia , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/patologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Homeostase , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/metabolismo
12.
Eur J Clin Microbiol Infect Dis ; 39(7): 1209-1220, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32328850

RESUMO

To analyze the susceptibility of SARS-CoV-2 in pregnancy and the drugs that can be used to treat pregnancy with COVID-19, so as to provide evidence for drug selection in clinic. By reviewing the existing literature, this paper analyzes the susceptibility of pregnant women to virus, especially to SARS-CoV-2, from the aspects of anatomical, reproductive endocrine and immune changes during pregnancy and screens effective and fetal-safe treatments from the existing drugs. The anatomical structure of the respiratory system is changed during pregnancy, and the virus transmitted by droplets and aerosols is more easily inhaled by pregnant women and is difficult to remove. Furthermore, the prognosis is worse after infection when compared with non-pregnancy women. And changes in reproductive hormones and immune systems during pregnancy collectively make them more susceptible to certain infections. More importantly, angiotensin-converting enzyme (ACE)-2, the SARS-CoV-2 receptor, has been proven highly increased during pregnancy, which may contribute to the susceptibility to SARS-CoV-2. When it comes to treatment, specific drugs for COVID-19 have not been found at present, and taking old drugs for new use in treating COVID-19 has become an emergency method for the pandemic. Particularly, drugs that show superior maternal and fetal safety are worthy of consideration for pregnant women with COVID-19, such as chloroquine, metformin, statins, lobinavir/ritonavir, glycyrrhizic acid, and nanoparticle-mediated drug delivery (NMDD), etc. Pregnant women are susceptible to COVID-19, and special attention should be paid to the selection of drugs that are both effective for maternal diseases and friendly to the fetus. However, there are still many deficiencies in the study of drug safety during pregnancy, and broad-spectrum, effective and fetal-safe drugs for pregnant women need to be developed so as to cope with more infectious diseases in the future.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Infecções por Coronavirus/metabolismo , Pneumonia Viral/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Gravidez/fisiologia , Fenômenos Fisiológicos Respiratórios , Anti-Inflamatórios/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Metabolismo Basal , Betacoronavirus/metabolismo , Cloroquina/uso terapêutico , Anormalidades Congênitas/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/metabolismo , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Feminino , Capacidade Residual Funcional , Ácido Glicirrízico/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/uso terapêutico , Interferon Tipo I/uso terapêutico , Lopinavir/uso terapêutico , Metformina/uso terapêutico , Nanopartículas , Consumo de Oxigênio , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Gravidez/imunologia , Gravidez/metabolismo , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/imunologia , Progesterona/metabolismo , Prognóstico , Ritonavir/uso terapêutico , Glicoproteína da Espícula de Coronavírus/metabolismo , Natimorto/epidemiologia , Relação Ventilação-Perfusão
13.
Pregnancy Hypertens ; 20: 69-74, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32193148

RESUMO

OBJECTIVES: To immuno-localize histone H2A expression as a marker of neutrophil extracellular traps (NETs) in the placenta; and to quantify and compare the percentage H2A immune-expression as a marker of NETs in the placental intervillous space according to: pregnancy type, HIV status and across the study population. STUDY DESIGN: The participants to the study were a pregnant South African population group of African ancestry (n = 60) stratified as normotensive (N) (n = 30) or pre-eclamptic (PE) (n = 30) and further subdivided as HIV infected (HIV+) (n = 15) or HIV naïve (HIV-) (n = 15). Following informed consent placental tissue samples were obtained at the time of delivery. Immunohistochemistry using the anti-histone 2A (H2A) antibody as a biomarker of NETs, and morphometric image analysis was used to immuno-localize and quantify placental H2A immuno-expression respectively in the placental inter-villous space. Statistical analysis was performed using Graph Pad Prism software (Version 5). MAIN OUTCOME MEASURES: To determine if HIV neutralizes the elevated NETs in PE. RESULTS: NETs were localized within the inter-villous space surrounding the exchange villi and conducting villi of placental tissue. Based on HIV status, a significant elevation in H2A immuno-expression was observed in the HIV+ compared to the HIV- group (p = 0.0008) and in the pre-eclampsia HIV- compared to the normotensive HIV- group (p = 0.0008). However, a significant decline in H2A immuno-expression was observed in the PEHIV+ group compared to the NHIV+ group (p = 0.0072). CONCLUSIONS: Both PE and HIV elevate placental NETs; however, they synergistically downregulate NETs expression. Further investigations are required to interrogate the signaling pathways involved to establish potential NET-targeted therapeutic actions.


Assuntos
Armadilhas Extracelulares/química , Infecções por HIV/metabolismo , Placenta/química , Pré-Eclâmpsia/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Adolescente , Adulto , Biomarcadores/análise , Vilosidades Coriônicas/química , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/fisiopatologia , Histonas/análise , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/fisiopatologia , África do Sul , Adulto Jovem
14.
J Virol ; 94(11)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188737

RESUMO

Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n = 6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n = 3 for FP isolate H/PF/2013; n = 3 for PR isolate PRVABC59) at midgestation (86 to 95 days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n = 5) or 39 days (n = 1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.


Assuntos
Doenças dos Macacos , Complicações Infecciosas na Gravidez , Sêmen/virologia , Vagina/virologia , Infecção por Zika virus , Zika virus/metabolismo , Animais , Feminino , Masculino , Doenças dos Macacos/metabolismo , Doenças dos Macacos/patologia , Doenças dos Macacos/transmissão , Doenças dos Macacos/virologia , Papio anubis , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/veterinária , RNA Viral/metabolismo , Vagina/patologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/veterinária
15.
PLoS Pathog ; 16(2): e1007968, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32059027

RESUMO

Human cytomegalovirus (HCMV) infection is the leading non-genetic cause of congenital birth defects worldwide. While several studies have addressed the genetic composition of viral populations in newborns diagnosed with HCMV, little is known regarding mother-to-child viral transmission dynamics and how therapeutic interventions may impact within-host viral populations. Here, we investigate how preexisting CMV-specific antibodies shape the maternal viral population and intrauterine virus transmission. Specifically, we characterize the genetic composition of CMV populations in a monkey model of congenital CMV infection to examine the effects of passively-infused hyperimmune globulin (HIG) on viral population genetics in both maternal and fetal compartments. In this study, 11 seronegative, pregnant monkeys were challenged with rhesus CMV (RhCMV), including a group pretreated with a standard potency HIG preparation (n = 3), a group pretreated with a high-neutralizing potency HIG preparation (n = 3), and an untreated control group (n = 5). Targeted amplicon deep sequencing of RhCMV glycoprotein B and L genes revealed that one of the three strains present in the viral inoculum (UCD52) dominated maternal and fetal viral populations. We identified minor haplotypes of this strain and characterized their dynamics. Many of the identified haplotypes were consistently detected at multiple timepoints within sampled maternal tissues, as well as across tissue compartments, indicating haplotype persistence over time and transmission between maternal compartments. However, haplotype numbers and diversity levels were not appreciably different between control, standard-potency, and high-potency pretreatment groups. We found that while the presence of maternal antibodies reduced viral load and congenital infection, it had no apparent impact on intrahost viral genetic diversity at the investigated loci. Interestingly, some minor haplotypes present in fetal and maternal-fetal interface tissues were also identified as minor haplotypes in corresponding maternal tissues, providing evidence for a loose RhCMV mother-to-fetus transmission bottleneck even in the presence of preexisting antibodies.


Assuntos
Anticorpos Antivirais/farmacologia , Infecções por Citomegalovirus , Citomegalovirus/metabolismo , Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez , Animais , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/metabolismo , Infecções por Citomegalovirus/patologia , Feminino , Macaca mulatta , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia
16.
Am J Obstet Gynecol ; 222(6): 610.e1-610.e13, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31954155

RESUMO

BACKGROUND: Zika virus infection during pregnancy can cause serious birth defects, which include brain and eye abnormalities. The clinical importance of detection of Zika virus RNA in amniotic fluid is unknown. OBJECTIVE: The purpose of this study was to describe patterns of Zika virus RNA testing of amniotic fluid relative to other clinical specimens and to examine the association between Zika virus detection in amniotic fluid and Zika-associated birth defects. Our null hypothesis was that Zika virus detection in amniotic fluid was not associated with Zika-associated birth defects. STUDY DESIGN: We conducted a retrospective cohort analysis of women with amniotic fluid specimens submitted to Colombia's National Institute of Health as part of national Zika virus surveillance from January 2016 to January 2017. Specimens (maternal serum, amniotic fluid, cord blood, umbilical cord tissue, and placental tissue) were tested for the presence of Zika virus RNA with the use of a singleplex or multiplex real-time reverse transcriptase-polymerase chain reaction assay. Birth defect information was abstracted from maternal prenatal and infant birth records and reviewed by expert clinicians. Chi-square and Fisher's exact tests were used to compare the frequency of Zika-associated birth defects (defined as brain abnormalities [with or without microcephaly, but excluding neural tube defects and their associated findings] or eye abnormalities) by frequency of detection of Zika virus RNA in amniotic fluid. RESULTS: Our analysis included 128 women with amniotic fluid specimens. Seventy-five women (58%) had prenatally collected amniotic fluid; 42 women (33%) had amniotic fluid collected at delivery, and 11 women (9%) had missing collection dates. Ninety-one women had both amniotic fluid and other clinical specimens submitted for testing, which allowed for comparison across specimen types. Of those 91 women, 68 had evidence of Zika virus infection based on detection of Zika virus RNA in ≥1 specimen. Testing of amniotic fluid that was collected prenatally or at delivery identified 39 of these Zika virus infections (57%; 15 [22%] infections were identified only in amniotic fluid), and 29 infections (43%) were identified in other specimen types and not amniotic fluid. Among women who were included in the analysis, 89 had pregnancy outcome information available, which allowed for the assessment of the presence of Zika-associated birth defects. Zika-associated birth defects were significantly (P<.05) more common among pregnancies with Zika virus RNA detected in amniotic fluid specimens collected prenatally (19/32 specimens; 59%) than for those with no laboratory evidence of Zika virus infection in any specimen (6/23 specimens; 26%), but the proportion was similar in pregnancies with only Zika virus RNA detected in specimens other than amniotic fluid (10/23 specimens; 43%). Although Zika-associated birth defects were more common among women with any Zika virus RNA detected in amniotic fluid specimens (ie, collected prenatally or at delivery; 21/43 specimens; 49%) than those with no laboratory evidence of Zika virus infection (6/23 specimens; 26%), this comparison did not reach statistical significance (P=.07). CONCLUSION: Testing of amniotic fluid provided additional evidence for maternal diagnosis of Zika virus infection. Zika-associated birth defects were more common among women with Zika virus RNA that was detected in prenatal amniotic fluid specimens than women with no laboratory evidence of Zika virus infection, but similar to women with Zika virus RNA detected in other, nonamniotic fluid specimen types.


Assuntos
Líquido Amniótico/virologia , Encéfalo/anormalidades , Anormalidades do Olho/epidemiologia , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/metabolismo , RNA Viral/metabolismo , Infecção por Zika virus/metabolismo , Zika virus/genética , Adulto , Líquido Amniótico/metabolismo , Estudos de Coortes , Colômbia/epidemiologia , Feminino , Sangue Fetal/metabolismo , Sangue Fetal/virologia , Humanos , Recém-Nascido , Malformações do Sistema Nervoso/epidemiologia , Placenta/metabolismo , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Cordão Umbilical/metabolismo , Cordão Umbilical/virologia , Adulto Jovem , Infecção por Zika virus/epidemiologia
17.
Sci Rep ; 10(1): 1082, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974453

RESUMO

Human cytomegalovirus (CMV) is the leading non-genetic cause of fetal malformation in developed countries. CMV placental infection is a pre-requisite for materno-fetal transmission of virus, and fetal infection. We investigated the roles of the viral pentameric complex gH/gL/pUL128-pUL131A, and cellular platelet-derived growth factor receptor-α (PDGFRα) for CMV infection in first trimester extravillous-derived (SGHPL-4) and villous-derived (HTR-8/SVneo) trophoblast cells. Infection with four CMV clinical and laboratory strains (Merlin, TB40E, Towne, AD169), and Merlin deletion mutants of UL128-, UL130-, and UL131A-genes, showed a cell type-dependent requirement of the viral pentameric complex for infection of trophoblast cells. The viral pentameric complex was essential for infection of villous trophoblasts, but non-essential for extravillous trophoblasts. Blocking of PDGFRα in extravillous trophoblasts, which naturally express PDGFRα, inhibited entry of pentameric complex-deficient CMV strains, but not the entry of pentameric positive CMV strains. Transient expression of PDGFRα in villous trophoblasts, which are naturally deficient in PDGFRα, promoted the entry of CMV strains lacking gH/gL/pUL128-pUL131A, but had no effect on entry of pentameric positive CMV strains. These results suggest PDGFRα is an important cell receptor for entry of CMV mutant strains lacking gH/gL/pUL128-pUL131A complexes in some placental cells, suggesting these entry pathways could be potential antiviral targets.


Assuntos
Infecções por Citomegalovirus/metabolismo , Citomegalovirus/fisiologia , Complicações Infecciosas na Gravidez/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Trofoblastos/metabolismo , Internalização do Vírus , Linhagem Celular , Citomegalovirus/genética , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Placenta/citologia , Placenta/metabolismo , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/genética , Complicações Infecciosas na Gravidez/virologia , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Trofoblastos/virologia , Proteínas do Envelope Viral/genética , Proteínas do Envelope Viral/metabolismo
18.
Viruses ; 12(1)2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861492

RESUMO

The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and immunological barrier preventing maternal-fetal transmission of pathogens. Several viruses can circumvent this physical barrier and enter the fetal compartment, resulting in miscarriage, preterm birth, and birth defects, including microcephaly. The mechanisms underlying viral strategies to evade the protective role of placenta are poorly understood. Here, we reviewed the role of trophoblasts and Hofbauer cells in the placenta and have highlighted characteristics of vertical and perinatal infections caused by a wide range of viruses. Moreover, we explored current progress and future opportunities in cellular targets, pathogenesis, and underlying biological mechanisms of congenital viral infections, as well as novel research models and tools to study the placenta.


Assuntos
Suscetibilidade a Doenças , Transmissão Vertical de Doença Infecciosa , Placenta/virologia , Complicações Infecciosas na Gravidez/virologia , Viroses/etiologia , Viroses/transmissão , Animais , Biomarcadores , Modelos Animais de Doenças , Feminino , Interações Hospedeiro-Patógeno , Humanos , Placenta/imunologia , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Pesquisa , Viroses/metabolismo
19.
PLoS Pathog ; 15(11): e1008038, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31725819

RESUMO

Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.


Assuntos
Encéfalo/patologia , Doenças Fetais/epidemiologia , Feto/virologia , Interferon-alfa/metabolismo , Complicações Infecciosas na Gravidez/epidemiologia , Útero/virologia , Infecção por Zika virus/virologia , Animais , Antivirais/metabolismo , Encéfalo/metabolismo , Encéfalo/virologia , Doenças Transmissíveis/transmissão , Doenças Transmissíveis/virologia , Feminino , Doenças Fetais/metabolismo , Doenças Fetais/virologia , Feto/metabolismo , Feto/patologia , Masculino , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/virologia , Fatores Sexuais , Suínos , Útero/metabolismo , Útero/patologia , Zika virus/patogenicidade , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/veterinária
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(9): 1071-1076, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31594148

RESUMO

Objective: To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of HBV. Methods: A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥10(3) copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 10(3)-10(6) copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01). Conclusions: IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥10(3) copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.


Assuntos
Hepatite B/metabolismo , Interleucina-18/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Estudos de Casos e Controles , Criança , Correlação de Dados , DNA Viral , Feminino , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Vírus da Hepatite B , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Gravidez , Complicações Infecciosas na Gravidez/virologia
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