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1.
Metabolomics ; 19(4): 41, 2023 04 15.
Article in English | MEDLINE | ID: covidwho-2304970

ABSTRACT

INTRODUCTION: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. OBJECTIVES: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. METHODS: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. RESULTS: Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725-0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. CONCLUSION: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population.


Subject(s)
COVID-19 , Fetal Blood , Pregnancy , Infant, Newborn , Female , Humans , Fetal Blood/chemistry , Metabolomics/methods , Fetus/metabolism , Prenatal Care
3.
Eur Rev Med Pharmacol Sci ; 27(6): 2692-2698, 2023 03.
Article in English | MEDLINE | ID: covidwho-2266621

ABSTRACT

OBJECTIVE: COVID-19 is a disease that affects and damages the neurological system. The aim of this study was to evaluate the fetal neurodevelopmental status through maternal serum and umbilical cord BDNF levels. PATIENTS AND METHODS: In this prospective study, 88 pregnant women were evaluated. Demographic and peripartum characteristics of the patients were recorded. Samples were collected from pregnant women for maternal serum and the umbilical cord BDNF levels during delivery. RESULTS: In this study, 40 pregnant women hospitalized with COVID-19 formed the infected group and 48 pregnant women without COVID-19 formed the healthy control group. Demographic and postpartum characteristics were similar in both groups. Maternal serum BDNF values were significantly lower in the COVID-19 infected group (1597.0 ± 337.3 pg/ml) than in the healthy group (1783.2 ± 394.1 pg/ml) (p=0.019). Fetal BDNF levels were 1794.9 ± 440.3 pg/ml in the healthy group and 1691.0 ± 368.6 pg/ml in COVID-19 infected pregnant women group and statistically similar between groups (p=0.232). CONCLUSIONS: Results showed that while maternal serum BDNF levels decreased in the presence of COVID-19, there was no difference in umbilical cord BDNF levels. This may be an indication that the fetus is not affected and is protected.


Subject(s)
Brain-Derived Neurotrophic Factor , COVID-19 , Humans , Pregnancy , Female , Prospective Studies , Fetal Blood , Umbilical Cord
4.
Int J Gynaecol Obstet ; 161(1): 308-313, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2173003

ABSTRACT

OBJECTIVE: To compare umbilical cord blood pro-B-type natriuretic peptide (BNP) levels in newborns of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) positive pregnancies to those of SARS-COV-2 negative pregnancies. METHODS: Prospectively cord blood samples from newborns of 42 SARS-COV-2 positive women, and 42 negative pregnant were collected at birth and analyzed for pro-BNP levels. RESULTS: The mean cord blood pro-BNP level was significantly higher in newborns of SARS-COV-2 positive women than in controls. Furthermore, the pro-BNP level was an independent predictor of NICU admission in both SARS-COV-2 positive and control patients. CONCLUSION: Cord blood pro-BNP level may be a parameter that can predict the under-stress fetus and adverse perinatal outcomes especially, in cases where placental involvement is present as in SARS-COV-2 infection.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Infant, Newborn , Pregnancy , Fetal Blood , Infectious Disease Transmission, Vertical , Natriuretic Peptide, Brain , Placenta , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2
5.
J Cell Mol Med ; 27(2): 222-231, 2023 01.
Article in English | MEDLINE | ID: covidwho-2192724

ABSTRACT

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 µg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.


Subject(s)
Exosomes , Extracellular Vesicles , Melanoma , MicroRNAs , Humans , Exosomes/metabolism , Fetal Blood/metabolism , MicroRNAs/metabolism , Melanoma/genetics , Extracellular Vesicles/metabolism , Stem Cells/metabolism
6.
Pediatr Res ; 92(1): 255-264, 2022 07.
Article in English | MEDLINE | ID: covidwho-2016650

ABSTRACT

INTRODUCTION: Maternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment. METHODS: Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group. RESULTS: Three hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment. CONCLUSION: The significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function. IMPACT: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer.


Subject(s)
Docosahexaenoic Acids , Placenta , Dietary Supplements , Female , Fetal Blood , Humans , Infant , Pregnancy , Prenatal Care , Vitamins
7.
Bull Exp Biol Med ; 173(4): 523-528, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-2007182

ABSTRACT

The study included umbilical cord blood samples (n=64) intended for cryogenic storage of hematopoietic stem cells and obtained from patients with a history of mild and moderate forms of COVID-19 during pregnancy. The control group was composed of samples (n=746) obtained from healthy women in labor. A comparative analysis of the volume of cord blood collected, the total leukocyte count, the relative and absolute content of cells with the CD34+/CD45+ phenotype revealed no significant differences between the groups.


Subject(s)
COVID-19 , Fetal Blood , Antigens, CD34 , Female , Fetal Blood/chemistry , Hematopoietic Stem Cells , Humans , Pregnancy
9.
Stem Cell Res Ther ; 13(1): 408, 2022 08 12.
Article in English | MEDLINE | ID: covidwho-2002225

ABSTRACT

BACKGROUND: The increasing number of clinical trials for induced pluripotent stem cell (iPSC)-derived cell therapy products makes the production on clinical grade iPSC more and more relevant and necessary. Cord blood banks are an ideal source of young, HLA-typed and virus screened starting material to produce HLA-homozygous iPSC lines for wide immune-compatibility allogenic cell therapy approaches. The production of such clinical grade iPSC lines (haplolines) involves particular attention to all steps since donor informed consent, cell procurement and a GMP-compliant cell isolation process. METHODS: Homozygous cord blood units were identified and quality verified before recontacting donors for informed consent. CD34+ cells were purified from the mononuclear fraction isolated in a cell processor, by magnetic microbeads labelling and separation columns. RESULTS: We obtained a median recovery of 20.0% of the collected pre-freezing CD34+, with a final product median viability of 99.1% and median purity of 83.5% of the post-thawed purified CD34+ population. CONCLUSIONS: Here we describe our own experience, from unit selection and donor reconsenting, in generating a CD34+ cell product as a starting material to produce HLA-homozygous iPSC following a cost-effective and clinical grade-compliant procedure. These CD34+ cells are the basis for the Spanish bank of haplolines envisioned to serve as a source of cell products for clinical research and therapy.


Subject(s)
Induced Pluripotent Stem Cells , Antigens, CD34/genetics , Antigens, CD34/metabolism , Blood Banks , Fetal Blood , Homozygote , Induced Pluripotent Stem Cells/metabolism
10.
Clin Chem Lab Med ; 60(9): 1486-1491, 2022 08 26.
Article in English | MEDLINE | ID: covidwho-1910717

ABSTRACT

OBJECTIVES: Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72 h. RESULTS: The median presepsin value in umbilical cord blood samples collected after birth was 455 pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5 days had a significantly higher presepsin level at birth rather than those discharged up to 4 days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48 h. CONCLUSIONS: This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.


Subject(s)
COVID-19 , Adult , COVID-19/diagnosis , Female , Fetal Blood , Humans , Infant, Newborn , Infant, Premature , Infectious Disease Transmission, Vertical , Lipopolysaccharide Receptors , Peptide Fragments , Pregnancy , SARS-CoV-2
11.
Obstet Gynecol ; 139(3): 373-380, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1864995

ABSTRACT

OBJECTIVE: To describe maternal and umbilical cord blood anti-spike immunoglobulin (Ig)G levels at delivery with coronavirus disease 2019 (COVID-19) vaccination before and during pregnancy and to assess the association of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a vaccine booster dose with anti-spike maternal and umbilical cord IgG levels. METHODS: We conducted a retrospective cohort study of women with self-reported COVID-19 vaccination (Pfizer-BioNTech, Moderna, or Johnson & Johnson/Janssen), including a booster dose, during or before pregnancy, who delivered at 34 weeks of gestation or more. Maternal and umbilical cord blood samples at delivery were analyzed for semi-quantitative anti-spike IgG. We examined the association between timing of maternal vaccination and maternal and umbilical cord anti-spike levels using a rank sum test. The relationships between a prior history of SARS-CoV-2 infection and maternal and umbilical cord anti-spike IgG levels, and between a booster dose and maternal and umbilical cord anti-spike levels, were also evaluated using a rank sum test. RESULTS: We included data from 1,359 vaccinated pregnant women, including 20 women who received a booster dose, and 1,362 umbilical cord samples. Maternal anti-spike IgG levels were detectable at delivery regardless of timing of vaccination throughout pregnancy among fully vaccinated women; however, early third-trimester vaccination was associated with the highest anti-spike IgG levels in maternal and umbilical cord blood. Among women with a history of SARS-CoV-2 infection, maternal and cord blood antibody response achieved with vaccination in early pregnancy was comparable with third-trimester vaccination in pregnant women without a history of SARS-CoV-2 infection. A booster dose in the third trimester was associated with maternal anti-spike IgG levels greater than third-trimester vaccination in women with or without a history of SARS-CoV-2 infection. DISCUSSION: Vaccination against COVID-19 before and throughout pregnancy was associated with detectable maternal anti-spike IgG levels at delivery. A complete vaccination course, prior history of SARS-CoV-2 infection, and a third-trimester booster dose were associated with the highest maternal and umbilical cord antibody levels.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , Fetal Blood/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , Adult , Female , Humans , Immunization, Secondary , Pregnancy , Retrospective Studies
12.
East. Mediterr. health j ; 28(5): 319-391, 2022-05.
Article in English | WHOIRIS | ID: gwh-355454

ABSTRACT

Eastern Mediterranean Health Journal is the official health journal published by the Eastern Mediterranean Regional Office of the World Health Organization. It is a forum for the presentation and promotion of new policies and initiatives in health services; and for the exchange of ideas concepts epidemiological data research findings and other information with special reference to the Eastern Mediterranean Region. It addresses all members of the health profession medical and other health educational institutes interested NGOs WHO Collaborating Centres and individuals within and outside the Region


المجلة الصحية لشرق المتوسط هى المجلة الرسمية التى تصدرعن المكتب الاقليمى لشرق المتوسط بمنظمة الصحة العالمية. وهى منبر لتقديم السياسات والمبادرات الجديدة فى الصحة العامة والخدمات الصحية والترويج لها، و لتبادل الاراء و المفاهيم والمعطيات الوبائية ونتائج الابحاث وغير ذلك من المعلومات، و خاصة ما يتعلق منها باقليم شرق المتوسط. وهى موجهة الى كل اعضاء المهن الصحية، والكليات الطبية وسائر المعاهد التعليمية، و كذا المنظمات غير الحكومية المعنية، والمراكز المتعاونة مع منظمة الصحة العالمية والافراد المهتمين بالصحة فى الاقليم و خارجه


La Revue de Santé de la Méditerranée Orientale est une revue de santé officielle publiée par le Bureau régional de l’Organisation mondiale de la Santé pour la Méditerranée orientale. Elle offre une tribune pour la présentation et la promotion de nouvelles politiques et initiatives dans le domaine de la santé publique et des services de santé ainsi qu’à l’échange d’idées de concepts de données épidémiologiques de résultats de recherches et d’autres informations se rapportant plus particulièrement à la Région de la Méditerranée orientale. Elle s’adresse à tous les professionnels de la santé aux membres des instituts médicaux et autres instituts de formation médico-sanitaire aux ONG Centres collaborateurs de l’OMS et personnes concernés au sein et hors de la Région.


Subject(s)
Environment and Public Health , Tobacco Smoke Pollution , COVID-19 , Disease Outbreaks , Betacoronavirus , Mental Health , Cesarean Section , Fetal Blood , Breast Feeding , Education, Medical , Schools, Medical , Ethics Committees, Research
13.
Cell Prolif ; 55(4): e13204, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1685252

ABSTRACT

OBJECTIVES: The impacts of the current COVID-19 pandemic on maternal and foetal health are enormous and of serious concern. However, the influence of SARS-CoV-2 infection at early-to-mid gestation on maternal and foetal health remains unclear. MATERIALS AND METHODS: Here, we report the follow-up study of a pregnant woman of her whole infective course of SARS-CoV-2, from asymptomatic infection at gestational week 20 to mild and then severe illness state, and finally cured at Week 24. Following caesarean section due to incomplete uterine rupture at Week 28, histological examinations on the placenta and foetal tissues as well as single-cell RNA sequencing (scRNA-seq) for the placenta were performed. RESULTS: Compared with the gestational age-matched control placentas, the placenta from this COVID-19 case exhibited more syncytial knots and lowered expression of syncytiotrophoblast-related genes. The scRNA-seq analysis demonstrated impaired trophoblast differentiation, activation of antiviral and inflammatory CD8 T cells, as well as the tight association of increased inflammatory responses in the placenta with complement over-activation in macrophages. In addition, levels of several inflammatory factors increased in the placenta and foetal blood. CONCLUSION: These findings illustrate a systematic cellular and molecular signature of placental insufficiency and immune activation at the maternal-foetal interface that may be attributed to SARS-CoV-2 infection at the midgestation stage, which highly suggests the extensive care for maternal and foetal outcomes in pregnant women suffering from COVID-19.


Subject(s)
COVID-19 , Cesarean Section , Female , Fetal Blood , Follow-Up Studies , Humans , Pandemics , Placenta , Pregnancy , Pregnant Women , SARS-CoV-2
14.
Int J Environ Res Public Health ; 19(4)2022 Feb 13.
Article in English | MEDLINE | ID: covidwho-1686780

ABSTRACT

OBJECTIVE: There are few data on the maternal-fetal transmission of SARS-CoV-2 and its outcomes. This study aimed to evaluate pregnancy outcomes of pregnant women infected by SARS-CoV-2, to detect SARS-CoV-2 in placenta and different newborns' samples and search antibodies in cord blood. METHODS: This was a prospective study of pregnant women diagnosed with SARS-CoV-2 infection from May 2020 to May 2021. At delivery, the placentas were investigated for SARS-CoV-2 using RT-PCR, cord blood. Mothers' blood samples were tested by SARS-CoV-2 serology. PCR of nasopharyngeal, anal and gastric swabs (NPSs) of newborns was performed according to pediatric indications. RESULTS: Among 3626 pregnant women presenting at maternity to deliver, 45 mothers had COVID-19 during their pregnancy or at delivery (32 ± 4.8 years). Most of them were multiparous and in the third trimester. There were 35 (77%) women who remained in ambulatory, while 10 (22%) were hospitalized for severe pneumonia, digestive symptoms, and/or fetal tachycardia. Thirty-eight delivered vaginally, and 7 had a cesarean delivery with normal Apgar scores (9 ± 1.6 at 5 min) and umbilical artery pH (7.22 ± 0.08). Two mothers required ICU admission after cesarean section for fetal and maternal distress. Of the 46 newborns, 6 were premature births (13%) and 5 IUGR (intra-uterine growth restriction,11%). RT-PCR SARS-CoV-2 was positive for 1/30 placental, and 1/33 neonatal anal swabs and negative in all other cases and in gastric swabs. SARS-CoV-2 IgG was positive in 20/41 cord blood samples (49%) and their mothers' samples. IgM was negative in the 23 cord blood samples. CONCLUSIONS: Pregnancy outcomes in women diagnosed with COVID-19 during their pregnancy were favorable in most cases. However, some women with severe clinical forms required hospitalization and ICU admission. Preterm births and intrauterine growth retardations were relatively frequent. Vaginal delivery was possible in most cases. SARS-CoV-2 IgG antibodies were positive and elevated in most cord blood samples of newborns. They are possibly of maternal origin, suggesting a probable mechanism of fetal protection against SARS-CoV-2 infection. No SARS-CoV-2 IgM was found in the cord blood samples. Detection of SARS-CoV-2 in placenta is rare.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/epidemiology , Cesarean Section , Child , Female , Fetal Blood , Humans , Immunoglobulin M , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2/genetics
15.
JAMA Pediatr ; 176(3): 290-295, 2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1589275

ABSTRACT

IMPORTANCE: BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in the third trimester was found to be associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn. OBJECTIVE: To evaluate maternal and neonatal SARS-CoV-2 immunoglobulin G (IgG) antibody levels at birth after mRNA COVID-19 vaccination during the second trimester of pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted at a single medical center in Haifa, Israel, from May to July 2021, included women with a singleton pregnancy over 24 weeks of gestation at least 7 days after receipt of their second COVID-19 vaccine dose who were not known to be previously infected with COVID-19. EXPOSURES: BNT162b2 (Pfizer/BioNTech) vaccination. MAIN OUTCOMES AND MEASURES: The primary outcomes were SARS-CoV-2 IgG antibody titers measured in the parturient at admission and in the umbilical cord blood within 30 minutes after delivery. Secondary outcomes were the correlation between antibody titers, feto-maternal characteristics, maternal adverse effects after vaccination, and time interval from vaccination to delivery. RESULTS: Antibody levels were measured for 129 women (mean [SD] age, 31.9 [4.9] years) and 114 neonates, with 100% of the tests having positive results. The mean (SD) gestational age at administration of the second vaccine dose was 24.9 (3.3) weeks. Neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1-17 643.5] AU/mL vs 1185.2 [146.6-32 415.1] AU/mL). A positive correlation was demonstrated between maternal and neonatal antibodies (r = 0.92; 95% CI, 0.89-0.94). Multivariable analysis revealed that for each week that passed since receipt of the second vaccine dose, maternal and neonatal antibody levels changed by -10.9% (95% CI, -17.2% to -4.2%; P = .002) and -11.7% (95% CI, -19.0 to -3.8%; P = .005), respectively. For each 1-year increase in the mother's age, maternal and neonatal antibody levels changed by -3.1% (95% CI, -5.3% to -0.9%; P = .007) and -2.7% (95% CI, -5.2% to -0.1%; P = .04), respectively. CONCLUSIONS AND RELEVANCE: In this cohort study, receipt of the BNT162b2 mRNA COVID-19 vaccine during the second trimester of pregnancy was associated with maternal and neonatal humoral responses, as reflected in maternal and neonatal SARS-CoV-2 IgG antibody levels measured after delivery. These findings support COVID-19 vaccination of pregnant individuals during the second trimester to achieve maternal protection and newborn safety during the pandemic.


Subject(s)
Antibody Formation , BNT162 Vaccine/administration & dosage , COVID-19/immunology , COVID-19/prevention & control , Immunity, Humoral , Immunoglobulin G/blood , Adult , Female , Fetal Blood/immunology , Humans , Infant, Newborn , Israel , Pregnancy , Pregnancy Trimester, Second , Prospective Studies , SARS-CoV-2
17.
J Infect Dis ; 224(Suppl 6): S647-S659, 2021 12 08.
Article in English | MEDLINE | ID: covidwho-1559634

ABSTRACT

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.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/diagnosis , Fetal Blood/immunology , Placenta/metabolism , SARS-CoV-2/immunology , Serine Endopeptidases/metabolism , Sex Factors , Adult , COVID-19/blood , Female , Fetal Blood/virology , Fetus/virology , Gene Expression , Humans , Infectious Disease Transmission, Vertical , Male , Pregnancy , Pregnancy Complications, Infectious/virology
18.
Int J Gynaecol Obstet ; 156(3): 436-443, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1525440

ABSTRACT

OBJECTIVE: To evaluate the correlation of maternal and cord blood levels of SARS-CoV-2 antibodies in pregnant women immunized against COVID-19. METHODS: A prospective cohort study was performed of pregnant women who delivered at a single university affiliated tertiary medical center. Women who received the COVID-19 vaccine (BNT162b2 Pfizer©) were approached. The correlation between levels of maternal sera and umbilical cord SARS-CoV-2 specific IgG was assessed. RESULTS: Overall, 58 women were included; of them, 19 had received a single dose and 39 received two doses of the COVID-19 vaccine. Positive levels of umbilical cord IgG were found in 13/19 (68.4%) and 38/39 (97.4%) women after the administration of a single dose and two doses of the vaccine, respectively. The levels of SARS-CoV-2 IgG antibodies in the maternal sera of vaccinated women were positively correlated to their respective concentrations in cord blood sera (ρ = 0.857; R2 linear = 0.719; P < 0.001). Thirteen days after vaccination, the ratio of maternal-to-umbilical cord anti Spike IgG antibodies was approximately 1, indicating relatively similar levels in maternal and cord sera. CONCLUSION: After the SARS-CoV-2 vaccine, levels of maternal and cord blood antibodies were positively correlated, especially when tested after 13 days following administration of the first dose of the vaccine.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , BNT162 Vaccine , Female , Fetal Blood , Humans , Pregnancy , Prospective Studies , SARS-CoV-2 , Vaccination
19.
STAR Protoc ; 2(4): 100903, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1514330

ABSTRACT

Determining how hematopoietic stem and progenitor cells (HSPCs) can be infected by viruses is necessary to understand and predict how the immune system will drive the host response. We present here a protocol to analyze the capacity of SARS-CoV-2 to infect different subsets of human HSPCs, inlcuding procedures for SARS-CoV-2 production and titration, isolation of human HSPCs from different sources (bone marrow, umbilical cord, or peripheral blood), and quantification of SARS-Cov-2 infection capacity by RT-qPCR and colony forming unit assay. For complete details on the use and execution of this protocol, please refer to Huerga Encabo et al. (2021).


Subject(s)
Bone Marrow/virology , COVID-19 Nucleic Acid Testing/methods , COVID-19/virology , Colony-Forming Units Assay/methods , Fetal Blood/virology , Hematopoietic Stem Cells/virology , SARS-CoV-2/isolation & purification , COVID-19/pathology , Hematopoietic Stem Cells/pathology , Humans
20.
Placenta ; 115: 146-150, 2021 11.
Article in English | MEDLINE | ID: covidwho-1514252

ABSTRACT

There is inadequate screening for SARS-COV-2 during pregnancy. We aimed to determine the impact of maternal and neonatal cord blood SARS-COV-2 antibodies and placental transfer ratios in a region with a low screening plan. We performed a blind study in one of the SARS-CoV-2 epicenters in South America. 32% of pregnant women were serological positive. Importantly, there is an efficient passive immunization of the fetus to SARS-CoV-2. We report high incidence of SARS-CoV-2 infection during pregnancy, which is higher than officially reported. Therefore the need of active immunization to enhance maternal protection and fetal passive immunization.


Subject(s)
COVID-19/epidemiology , Fetal Blood/immunology , Pregnancy Complications, Infectious/epidemiology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , Ecuador/epidemiology , Female , Fetal Blood/metabolism , Humans , Immunization, Passive/statistics & numerical data , Immunoglobulin G/blood , Immunoglobulin M/blood , Incidence , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Middle Aged , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/immunology , Seroepidemiologic Studies , Young Adult
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