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2.
J Infect Dis ; 224(12 Suppl 2): S670-S682, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33880544

RESUMO

BACKGROUND: Implementation of universal antiretroviral therapy (ART) has significantly lowered vertical transmission rates but has also increased numbers of human immunodeficiency virus (HIV)-exposed uninfected children, who remain vulnerable to morbid effects. In the current study, we investigated whether T-cell alterations in the placenta contribute to altered immune status in HIV-exposed uninfected. METHODS: We analyzed T cells from term placenta decidua and villous tissue and paired cord blood from pregnant women living with HIV (PWH) who initiated ART late in pregnancy (n = 21) with pregnant women not living with HIV (PWNH) (n = 9). RESULTS: Placentas from PWH showed inverted CD4/CD8 ratios and higher proportions of tissue resident CD8+ T cells in villous tissue relative to control placentas. CD8+ T cells in the fetal capillaries, which were of fetal origin, were positively correlated with maternal plasma viremia before ART initiation, implying that imbalanced T cells persisted throughout pregnancy. In addition, the expanded memory differentiation of CD8+ T cells was confined to the fetal placental compartment and cord blood but was not observed in the maternal decidua. CONCLUSIONS: T-cell homeostatic imbalance in the blood circulation of PWH is reflected in the placenta. The placenta may be a causal link between HIV-induced maternal immune changes during gestation and altered immunity in newborn infants in the absence of vertical transmission.


Assuntos
Sangue Fetal/virologia , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas , Placenta/patologia , Complicações Infecciosas na Gravidez , Feminino , HIV , Infecções por HIV/sangue , Humanos , Gravidez , Gestantes
3.
J Infect Dis ; 224(Suppl 6): S647-S659, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34293137

RESUMO

BACKGROUND: Expression of angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), host molecules required for viral entry, may underlie sex differences in vulnerability to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated whether placental ACE2 and TMPRSS2 expression vary by fetal sex in the presence of maternal SARS-CoV-2 infection. METHODS: Placental ACE2 and TMPRSS2 expression was quantified by quantitative reverse transcription polymerase chain reaction (RT-PCR) and by Western blot in 68 pregnant women (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. The impact of fetal sex and maternal SARS-CoV-2 exposure on ACE2 and TMPRSS2 was analyzed by 2-way analysis of variance (ANOVA). RESULTS: Maternal SARS-CoV-2 infection impacted placental TMPRSS2 expression in a sexually dimorphic fashion (2-way ANOVA interaction, P = .002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on ACE2. TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman ρ = 0.54, P = .02) but not females (ρ = 0.23, P = .34) exposed to maternal SARS-CoV-2. CONCLUSIONS: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection, which may have implications for offspring vulnerability to placental infection.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , Sangue Fetal/imunologia , Placenta/metabolismo , SARS-CoV-2/imunologia , Serina Endopeptidases/metabolismo , Fatores Sexuais , Adulto , COVID-19/sangue , Feminino , Sangue Fetal/virologia , Feto/virologia , Expressão Gênica , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia
4.
BMC Infect Dis ; 21(1): 716, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330230

RESUMO

BACKGROUND: Hepatitis B virus (HBV) remains a major global public health problem worldwide; in endemic areas, mother-to-child transmission (MTCT) of HBV is the most common transmission route. Previous studies have shown that amniocentesis for prenatal diagnosis increases the risk of MTCT of HBV among highly viraemic mothers. However, no data is available on MTCT related fetal blood sampling (FBS) because of the paucity of cases or lack of attention. We present a case series of HBV-infected women who underwent FBS with or without antiviral therapy during pregnancy and discuss the risk of MTCT after FBS. CASE PRESENTATION: Six hepatitis B surface antigen (HBsAg)-positive pregnant women who underwent FBS for prenatal diagnosis were retrospectively reviewed. Their infants were followed up with HBV serology parameters until at least 12 months of age. Among 6 cases, two hepatitis B e-antigen (HBeAg)-positive mothers had high viral loads > 7.0 log10 IU/mL, and one of them received antiviral therapy at 26+ 3 gestational weeks and achieved an anticipated level of 4.52 log10 IU/mL before FBS, while the other one did not receive any antiviral treatment. The other 4 cases were HBeAg-negative with low viral loads. Only a child born to the HBeAg-positive mother, who had no antiviral therapy with a viral load of 7.48 log10 IU/mL before FBS, was found to have MTCT with HBsAg persistently positive from birth to 12 months of age. The other 5 children were both HBsAg-negative and HBsAb-positive at the end of follow-up. CONCLUSIONS: FBS may increase the risk of MTCT of HBV in women with HBeAg-positive and high viral loads; therefore, FBS should be avoided in this high-risk population. Maternal HBV serologic testing and awareness of the potential risk of MTCT should be recommended before FBS. Antiviral therapy may be effective to decrease the risk of MTCT after FBS in highly viraemic women.


Assuntos
Sangue Fetal/virologia , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Adulto , Feminino , Hepatite B/diagnóstico , Hepatite B/terapia , Hepatite B/virologia , Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/virologia , Diagnóstico Pré-Natal , Estudos Retrospectivos , Fatores de Risco , Carga Viral , Viremia/terapia , Viremia/transmissão
5.
BMC Pregnancy Childbirth ; 21(1): 78, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482757

RESUMO

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.


Assuntos
COVID-19/fisiopatologia , Complicações Infecciosas na Gravidez/fisiopatologia , Aborto Espontâneo/epidemiologia , Adulto , Líquido Amniótico/virologia , COVID-19/mortalidade , COVID-19/transmissão , Fezes/virologia , Feminino , Sangue Fetal/virologia , Hospitalização/estatística & dados numéricos , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Estudos Longitudinais , Leite Humano/virologia , Estudos Observacionais como Assunto , Mortalidade Perinatal , Placenta/virologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Nascimento Prematuro/epidemiologia , SARS-CoV-2 , Espanha/epidemiologia , Urina/virologia
6.
Gac Med Mex ; 157(1): 29-34, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34125810

RESUMO

INTRODUCTION: Analysis of several parameters is required for adequate quality control in umbilical cord blood units (UCBU) when used for therapeutic purposes. OBJECTIVE: To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU. METHODS: One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the sequence-specific priming technique. RESULTS: CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p < 0.0001), as well as that of UCB in comparison with that of the segment (p < 0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY/11 and GP5/GP6+. CONCLUSIONS: Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.


INTRODUCCIÓN: Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos. OBJETIVO: Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU. MÉTODOS: Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming. RESULTADOS: La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p < 0.0001); así como la de SCU comparada con la de segmento (p < 0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+. CONCLUSIONES: Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.


Assuntos
DNA Viral/isolamento & purificação , Sangue Fetal/virologia , Genoma Viral , Células-Tronco Hematopoéticas/virologia , Papillomaviridae/isolamento & purificação , Adulto , Linhagem Celular , Criopreservação , Eletroforese em Gel de Ágar , Feminino , Sangue Fetal/citologia , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora) , Células HeLa , Teste de Histocompatibilidade , Humanos , Papillomaviridae/genética , Reação em Cadeia da Polimerase/métodos , Adulto Jovem
7.
Transfusion ; 60(5): 889-891, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32208533

RESUMO

Umbilical cord blood is an important cellular therapy product used for hematopoietic stem cell transplantation, but the US Food and Drug Administration guidance regarding donor screening to reduce the risk of Zika transmission has decreased the number of licensed, eligible cord blood units available for transplantation. There is a crucial need for updated travel risk assessment for Zika virus transmission, validated screening tests for Zika virus in umbilical cord blood, and further research on Zika virus transmissibility due to umbilical cord blood products to ensure that umbilical cord blood and related tissues are safe and available for transplantation.


Assuntos
Armazenamento de Sangue , Bancos de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Seleção do Doador , Transplante de Células-Tronco Hematopoéticas , Infecção por Zika virus/sangue , Infecção por Zika virus/epidemiologia , Bancos de Sangue/organização & administração , Bancos de Sangue/normas , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/normas , Seleção do Doador/organização & administração , Seleção do Doador/normas , Feminino , Sangue Fetal/transplante , Sangue Fetal/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Masculino , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Medição de Risco , Zika virus/fisiologia , Infecção por Zika virus/transmissão , Armazenamento de Sangue/métodos
8.
Am J Obstet Gynecol ; 223(1): 111.e1-111.e14, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32335053

RESUMO

BACKGROUND: The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series. OBJECTIVE: To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. RESULTS: The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/virologia , Aborto Espontâneo/virologia , Adulto , Líquido Amniótico/virologia , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/complicações , Feminino , Sangue Fetal/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Pandemias , Pneumonia Viral/complicações , Gravidez , Complicações Infecciosas na Gravidez/patologia , Resultado da Gravidez , Nascimento Prematuro/virologia , SARS-CoV-2
9.
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
10.
Ultrasound Obstet Gynecol ; 55(6): 835-837, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249471

RESUMO

Imaging modalities play a crucial role in the management of suspected COVID-19 patients. Before reverse transcription polymerase chain reaction (RT-PCR) test results are positive, 60-93% of patients have positive chest computed tomographic (CT) findings consistent with COVID-19. We report a case of positive lung ultrasound findings consistent with COVID-19 in a woman with an initially negative RT-PCR result. The lung ultrasound-imaging findings were present between the negative and subsequent positive RT-PCR tests and correlated with CT findings. The point-of-care lung-ultrasound examination was easy to perform and, as such, could play an important role in the triage of women with suspected COVID-19. The neonatal swabs, cord blood and placental swab RT-PCR tests were negative for SARS-CoV-2, a finding consistent with the published literature suggesting no vertical transmission of this virus in pregnant women. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , COVID-19 , Cesárea , Angiografia por Tomografia Computadorizada , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Diagnóstico Diferencial , Feminino , Sangue Fetal/virologia , Humanos , Leite Humano/virologia , Pandemias , Placenta/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Testes Imediatos , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Embolia Pulmonar/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada por Raios X
11.
J Infect Chemother ; 26(12): 1313-1315, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32859496

RESUMO

The coronavirus disease 2019 (COVID-19) has been a worldwide pandemic diseases, nearly 400,000 people died at now. The data of status of pregnant women and neonates after infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. We report a case of pregnant woman in her third trimester with critical COVID-19, and amniotic fluid, umbilical cord blood, placenta, and neonatal gastric fluid were retained during cesarean section. The SARS-COV-2 nucleic acid test results of these specimens were negative. There is no evidence of intrauterine vertical transmission during delivery in the third trimester, but the data are limited and need to be further explored.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Transmissão Vertical de Doenças Infecciosas , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Adulto , Líquido Amniótico/virologia , COVID-19 , Cesárea , Infecções por Coronavirus/complicações , Feminino , Sangue Fetal/virologia , Humanos , Recém-Nascido , Masculino , Pandemias , Placenta/virologia , Pneumonia Viral/complicações , Gravidez , Resultado da Gravidez , SARS-CoV-2 , Útero/virologia
12.
Transfusion ; 59(9): 2938-2951, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31251408

RESUMO

BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.


Assuntos
Vírus da Dengue/crescimento & desenvolvimento , Dengue/patologia , Dengue/transmissão , Células-Tronco Hematopoéticas/virologia , Ensaio de Placa Viral , Antígenos Virais/análise , Antígenos Virais/isolamento & purificação , Células da Medula Óssea/patologia , Células da Medula Óssea/fisiologia , Células da Medula Óssea/virologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Dengue/sangue , Vírus da Dengue/patogenicidade , Sangue Fetal/citologia , Sangue Fetal/virologia , Citometria de Fluxo , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Imunofenotipagem , Megacariócitos/patologia , Megacariócitos/fisiologia , Megacariócitos/virologia , Células Progenitoras Mieloides/patologia , Células Progenitoras Mieloides/fisiologia , Células Progenitoras Mieloides/virologia
13.
Biol Blood Marrow Transplant ; 23(10): 1729-1735, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28687394

RESUMO

Several studies have reported an impact of adult hematopoietic stem cell donor cytomegalovirus (CMV) serostatus on allogeneic hematopoietic cell transplantation outcomes. Limited data, however, are available on the impact of cord blood unit (CBU) CMV serostatus on allogeneic umbilical cord blood transplantation (UCBT) outcomes. We analyzed, retrospectively, the impact of CBU CMV serostatus on relapse incidence (RI) and 2-year nonrelapse mortality (NRM) of single-unit CBU transplantation for acute leukemia. Data from 1177 de novo acute leukemia pediatric and adult patients transplanted within European Group for Blood and Marrow Transplantation centers between 2000 and 2012 were analyzed. CBUs were provided by the European Cord Blood Banks. The median follow-up time for live patients was 59.9 months. The recipients of CMV-seropositive and -seronegative CBUs showed a comparable RI (33% versus 35%, respectively, P = .6) and 2-year cumulative incidence of NRM (31% versus 32%, respectively, P = .5). We conclude that CBU CMV serostatus did not influence RI and NRM in de novo acute leukemia patients after allo-UCBT and should not be included as a criteria for cord blood choice.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Citomegalovirus/patogenicidade , Sangue Fetal/virologia , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Humanos , Leucemia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
14.
Transfusion ; 57(11): 2768-2774, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28758211

RESUMO

BACKGROUND: The low incidence of cytomegalovirus (CMV) infection in neonates decreases the risk of viral transmission with cord blood transplantation. Cord blood donors are screened by testing the maternal sample for total antibodies to CMV. Some cord blood banks also screen cord blood for CMV-DNA. The aim of this study was to develop and validate a multiplex real-time polymerase chain reaction assay to measure CMV viral load in cord blood from asymptomatic infants with congenital CMV infection and to assess the impact of CMV infection on cord blood hematopoietic progenitor cell concentrations and colony-forming unit functionality. STUDY DESIGN AND METHODS: CMV infection was evaluated in two groups of cord blood donors: 1) 30,308 neonates prospectively screened by saliva culture, including 41 positive cases (0.14%), all from mothers with total antibodies to CMV; and 2) 4712 newborns from mothers with total antibodies to CMV who were screened retrospectively by polymerase chain reaction, including 18 positive cases (0.38%). All 59 infants with CMV were asymptomatic at birth. RESULTS: Among the 59 positive cases, the average CMV viral load in cord blood was 20.6 × 104 viral copies (vc)/mL; seven of 59 mothers (12%) had CMV-DNA detected, however, with no association to their newborns' CMV viral load. Levels of colony-forming units, CD34+ /CD45+ cells, and total nucleated cells measured in a cohort of CMV-positive cord blood samples were higher than those in the matched control group. CONCLUSION: We developed and validated a multiplex real-time polymerase chain reaction assay to detect CMV-DNA in cord blood. In our study, maternal total antibodies to CMV or CMV-DNA at birth were poor predictors of infection in cord blood donors. Furthermore, our results suggest that CMV congenital infection impacts CD34+ /CD45+ cells and some hematopoietic progenitor cells toward higher proliferation.


Assuntos
Doadores de Sangue , Infecções por Citomegalovirus/diagnóstico , DNA Viral/sangue , Sangue Fetal/virologia , Anticorpos Antivirais/sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/transmissão , Reações Falso-Negativas , Feminino , Células-Tronco Hematopoéticas/citologia , Humanos , Recém-Nascido , Limite de Detecção , Masculino , Mães , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral/métodos
15.
Virol J ; 14(1): 92, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28482844

RESUMO

BACKGROUND: TTV has been detected in almost every human tissue type or body fluid reaching near 100% prevalence. Several studies report mother-to-child postnatal transmission of TTV in infancy but the risk of transplacental transmission of TTV is still unclear. METHODS: The blood and plasma collected postpartum from 100 mother-child pairs were analyzed using TTV-specific qPCR. Samples were collected from the peripheral vein of the mother and the umbilical cord. RESULTS: Eighty four percent of pregnant women were TTV positive (median titers: 8 × 104 copies/mL; range: 103 - 3 × 107). The TTV load in plasma was approximately 100 times lower than in whole blood. TTV was not detected in any of cord blood samples. CONCLUSIONS: Our data demonstrate the lack of transplacental transmission of TTV (or effective prenatal inhibition of viral proliferation). The presence of the virus in infants may be associated with mother-to-child transmission through breast feeding or other routes of transmission.


Assuntos
Infecções por Vírus de DNA/transmissão , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/virologia , Torque teno virus/isolamento & purificação , Adulto , Infecções por Vírus de DNA/sangue , Infecções por Vírus de DNA/virologia , DNA Viral/sangue , Feminino , Sangue Fetal/virologia , Humanos , Lactente , Pessoa de Meia-Idade , Gravidez , Reação em Cadeia da Polimerase em Tempo Real , Federação Russa , Torque teno virus/genética , Torque teno virus/patogenicidade , Carga Viral
16.
Eur J Clin Microbiol Infect Dis ; 36(8): 1491-1503, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28324192

RESUMO

The purpose of this study was to evaluate if an early exposure to human papillomavirus (HPV) during the prenatal period or infancy could result in HPV16-specific T helper (Th) responses resembling those of adults with HPV-induced lesions. We tested HPV16-specific cell-mediated immunity (CMI) in children born with HPV-positive umbilical cord blood and/or placenta or having persistent oral HPV infection and in constantly oral HPV-negative controls. Peripheral blood mononuclear cells from 33 children from the Finnish HPV Family Study cohort (mean age 14.7 years) were stimulated with peptide pools covering the amino acid sequence of the HPV16 E2, E6, and E7 proteins. Lymphocyte proliferation, secretion of cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-5, IL-10, IL-17A), and the frequency of Foxp3+ regulatory T-cells were determined in relation to the HPV DNA status during a 14-year follow-up. 73.6% of cases and 85.7% of controls responded against HPV16 E2, while reactivity against E6 was found in 10.5 and 35.7%, respectively. The proliferative response against E6 and E7 was more frequent in controls than in cases (p = 0.047). No HPV16-specific CMI response or antibodies were detected in two children with persistent oral HPV16. The profiles of induced cytokines indicated higher levels of IL-5, IL-10, and IL-17A in children with HPV DNA in placenta and/or cord blood than in other children. HPV16-specific CMI is common in HPV DNA-negative children. The cytokine profile in children infected with HPV16 during early life suggests that the viral dose and/or specific environment created by the placenta may have significant impact on the type of HPV-specific immunity.


Assuntos
Sangue Fetal/virologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 16/isolamento & purificação , Troca Materno-Fetal , Placenta/virologia , Células Th2/imunologia , Adolescente , Antígenos Virais/imunologia , Proliferação de Células , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Finlândia , Seguimentos , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Boca/virologia , Gravidez
17.
Transpl Infect Dis ; 19(1)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27859994

RESUMO

Chromosomally integrated human herpesvirus 6 (ciHHV-6) can be transmitted via allogeneic hematopoietic cell transplantation. To date, only a few cases have been reported. Here, we report a case identified as transmission of ciHHV-6 via cord blood transplantation. Distinguishing transmission of ciHHV-6 from HHV-6 reactivation in cases with high titer of HHV-6 DNA load after transplantation is important to prevent unnecessary exposure to antiviral drugs that could be toxic.


Assuntos
Cromossomos Humanos Par 22/virologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Sangue Fetal/virologia , Herpesvirus Humano 6/genética , Agonistas Mieloablativos/efeitos adversos , Infecções por Roseolovirus/transmissão , Condicionamento Pré-Transplante/efeitos adversos , Integração Viral , Aciclovir/administração & dosagem , Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Antibioticoprofilaxia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Bussulfano/efeitos adversos , Bussulfano/uso terapêutico , Pré-Escolar , DNA Viral/isolamento & purificação , Exantema/sangue , Exantema/virologia , Febre/sangue , Febre/virologia , Herpesvirus Humano 6/isolamento & purificação , Humanos , Hospedeiro Imunocomprometido , Masculino , Melfalan/efeitos adversos , Melfalan/uso terapêutico , Agonistas Mieloablativos/uso terapêutico , Infecções por Roseolovirus/sangue , Infecções por Roseolovirus/genética , Infecções por Roseolovirus/virologia , Doadores não Relacionados , Valaciclovir , Valina/administração & dosagem , Valina/análogos & derivados , Valina/uso terapêutico , Carga Viral
18.
Prenat Diagn ; 37(4): 389-398, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28207161

RESUMO

OBJECTIVE: The objective of this study is to investigate the diagnostic value of invasive prenatal diagnosis (PD) of congenital cytomegalovirus (CMV) infection from amniotic fluid (AF) and fetal blood (FB). METHODS: A retrospective study was conducted on 115 pregnancies with CMV primary infection. A total of 111 AF and 106 FB samples were investigated for various virological and non-virological markers. Detailed ultrasound examinations were performed at time of PD. RESULTS: Overall sensitivity of CMV PCR in FB (75.6%; 95%CI 60-87) and AF (72.7%; 95%CI 57-85) was comparable. In women with amniocentesis >8 weeks between seroconversion and PD, we did not observe significant differences between amniocentesis performed ≥17 + 0 (sensitivity 90.9%; 95%CI 71-99) and ≥20 + 0 gestational weeks (sensitivity 90.0%; 95%CI 68-99). Virological markers in FB were higher in symptomatic compared with asymptomatic fetuses (p < 0.05). No significant differences were observed for non-virological markers. However, platelet counts <120 × 10e9/L and beta-2 microglobulin values >14 mg/L were more frequently found in fetuses with severe ultrasound abnormalities compared with fetuses with no or mild abnormalities (p < 0.001). CONCLUSION: Optimal timing of amniocentesis in women with primary infection in early gestation should be reevaluated in a prospective study. Analysis of FB markers may be beneficial in the individual management of pregnant women with confirmed congenital CMV infection. © 2017 John Wiley & Sons, Ltd.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Doenças Fetais/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Diagnóstico Pré-Natal , Adulto , Amniocentese , Infecções por Citomegalovirus/congênito , Feminino , Sangue Fetal/virologia , Doenças Fetais/virologia , Alemanha , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
19.
J Infect Dis ; 214(12): 1911-1915, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27703035

RESUMO

Human herpesvirus 6B (HHV-6B) commonly reactivates after umbilical cord blood transplantation (UCBT) and is associated with delayed engraftment, fever, rash, and central nervous system dysfunction. Recently, CD134 (OX40) has been implicated as a potential viral entry receptor. We evaluated CD4+CD134+/neg-lo and CD8+CD134+/neg-lo cells at day 28 after UCBT in 20 subjects with previously documented HHV-6 reactivation and persistent viremia. Analysis of CD4+CD134+ cells as compared to CD4+CD134neg-lo cells showed 0.308 versus 0.129 copies of HHV-6B/cell (P = .0002). CD8+CD134+/neg-lo cells contained little to no HHV-6B copies. Following UCBT, CD4+CD134+ cells harbor significantly increased levels of HHV-6B, suggesting that CD134 (OX40) may facilitate viral entry.


Assuntos
Linfócitos T CD4-Positivos/virologia , DNA Viral/análise , Sangue Fetal/virologia , Herpesvirus Humano 6/isolamento & purificação , Receptores OX40/análise , Infecções por Roseolovirus/virologia , Transplante/efeitos adversos , Adulto , Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Linfócitos T CD8-Positivos/virologia , Criança , Estudos de Coortes , DNA Viral/genética , DNA Viral/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Clin Infect Dis ; 62(7): 903-905, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26679622

RESUMO

We report 2 cases of Ebola viral disease (EVD) in pregnant women who survived, initially with intact pregnancies. Respectively 31-32 days after negativation of the maternal blood EVD-polymerase chain reaction (PCR) both patients delivered a stillborn fetus with persistent EVD-PCR amniotic fluid positivity.


Assuntos
Doença pelo Vírus Ebola , Complicações Infecciosas na Gravidez , Adulto , Líquido Amniótico/virologia , Feminino , Sangue Fetal/virologia , Humanos , Placenta/virologia , Gravidez , Natimorto , Adulto Jovem
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