Possible vertical transmission of Chikungunya virus infection detected in the cord blood samples from a birth cohort in Vietnam.

BACKGROUND: Chikungunya virus (CHIKV) is an alphavirus (genus Alphavirus, family Togaviridae) that is primarily transmitted to humans by Aedes mosquitoes, and can be transmitted from mother to child. Little is known about CHIKV transmission in Vietnam, where dengue is endemic and Aedes mosquitoes are abundant. This study aimed to determine the prevalence and characteristics of vertical CHIKV infection in a birth cohort, and seroprevalence of anti-CHIKV antibodies with or without confirmation by neutralization tests among women bearing children in Vietnam. METHODS: We collected umbilical cord blood plasma samples from each newly delivered baby in Nha Trang, Central Vietnam, between July 2017 and September 2018. Samples were subjected to molecular assay (quantitative real-time RT-PCR) and serological tests (anti-CHIKV IgM capture and IgG indirect enzyme-linked immunosorbent assay, and neutralization tests). RESULTS: Of the 2012 tested cord blood samples from newly delivered babies, the CHIKV viral genome was detected in 6 (0.3%) samples by RT-PCR, whereas, 15 samples (0.7%) were anti-CHIKV-IgM positive. Overall, 18 (0.9%, 95% CI: 0.6-1.5) samples, including three positives for both CHIKV IgM and viral genome on RT-PCR, were regarded as vertical transmission of CHIKV infection. Of the 2012 cord blood samples, 10 (0.5%, 95% CI: 0.2-0.9) were positive for both anti-CHIKV IgM and IgG. Twenty-nine (1.4%, 95% CI: 1.0-2.1) were seropositive for anti-CHIKV IgG while 26 (1.3%, 95% CI: 0.8-1.9) of them were also positive for neutralizing antibodies, and regarded as seropositive with neutralization against CHIKV infection. CONCLUSION: This is the first report of a possible CHIKV maternal-neonatal infection in a birth cohort in Vietnam. The findings indicate that follow-up and a differential diagnosis of CHIKV infection in pregnant women are needed to clarify the potential for CHIKV vertical transmission and its impact in the newborn.

Impact of FDA's HCT/P ZIKV Recommendations on Cord Blood Unit Eligibility and Utilization in a Large Public Cord Blood Bank.

BACKGROUND: Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. METHODS: We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). RESULTS: CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. DISCUSSION: The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.

Frequency and natural course of congenital cytomegalovirus-associated hearing loss in children.

BACKGROUND: Congenital cytomegalovirus-associated hearing loss (cCMV-associated HL) is a common cause of congenital or early-onset deafness. Although cCMV infection has been reported to lead to various types of HL, the natural course of cCMV-associated HL over a long period is not yet known. OBJECTIVES: To investigate the clinical phenotype of cCMV-associated HL in the largest study to date. METHODS: Thirty-one CMV-positive children, diagnosed by examining CMV DNA extracted from their dried umbilical cords retrospectively, were divided into unilateral and bilateral HL groups, and their hearing ability was evaluated using pure-tone audiometry and auditory steady-state response over time. RESULTS: Thirteen patients (41.9%) had unilateral HL and 18 (58.1%) had bilateral HL. In most cases of unilateral cCMV-associated HL, the ear with better hearing maintained a normal hearing threshold. Notably, in most cases of both unilateral and bilateral HL, the ear with worse hearing ultimately showed severe to profound HL. CONCLUSION: Our findings revealed that the natural course of cCMV-associated HL was different between the cases of unilateral and bilateral HL, as well as between the ears with better or worse hearing in all cases. These findings indicate that accurate diagnosis could enable proper follow-up and management of cCMV-associated HL in children.

Infecting human hematopoietic stem and progenitor cells with SARS-CoV-2.

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).

Risk of mother-to-child transmission of hepatitis B virus after fetal blood sampling: a report of six cases.

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.

Placental Expression of ACE2 and TMPRSS2 in Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Are Placental Defenses Mediated by Fetal Sex?

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.

Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study.

OBJECTIVE: To evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a descriptive, multicentre, observational study in nine tertiary care hospitals throughout Spain. The study population was women with coronavirus disease 2019 during pregnancy. Mother-to-child transmission was defined as positive real-time RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 women with singleton pregnancies and one with a twin pregnancy, as a result we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14-41.3 weeks). The median interval between positive RT-PCR and delivery was 21.5 days (range 0-141 days). Fourteen women (31.8%, 95% CI 18.6%-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95% CI 0.1%-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95% CI 0%-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95% CI 0.2%-41.3%). CONCLUSIONS: The presence of SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Colony-forming units optimization and human papillomavirus detection in umbilical cord blood.

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.

T-Cell Homeostatic Imbalance in Placentas From Women With Human Immunodeficiency Virus in the Absence of Vertical Transmission.

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.

Optimización de unidades formadoras de colonias y detección del virus de papiloma humano en sangre de cordón umbilical / Colony-forming units optimization and human papillomavirus detection in umbilical cord blood

Resumen 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.

Abstract Introduction: Analysis of several markers is required for adequate quality control in umbilical cord blood units (UCBU) when are 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 SSP 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/MY11 and GP5/GP6+. Conclusions: Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.

Postnatal IVIG treatment for persistent anaemia in neonate due to congenital parvovirus infection.

Congenital parvovirus B19 infection is a rare but serious condition that can result in hydrops fetalis and fetal death. Due to the virus' cytotoxic effect on fetal red blood cell precursors, postnatal infection can cause a neonatal viremia and secondary pure red cell aplasia. Here, we describe a case of congenital parvovirus infection in a preterm infant complicated by hydrops fetalis and chronic anaemia that responded to postnatal treatment with intravenous immunoglobulin administered on day of life 44. After treatment, the anaemia resolved as the neonate exhibited interval increases in haemoglobin, haematocrit and reticulocyte count with no subsequent need for red blood cell transfusions.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

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.

Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein.

Despite evidence that SARS-CoV-2 infection is systemic in nature, there is little known about the effects that SARS-CoV-2 infection or exposure has on many host cell types, including primitive and mature hematopoietic cells. The hematopoietic system is responsible for giving rise to the very immune cells that defend against viral infection and is a source of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) which are used for hematopoietic cell transplantation (HCT) to treat hematologic disorders, thus there is a strong need to understand how exposure to the virus may affect hematopoietic cell functions. We examined the expression of ACE2, to which SARS-CoV-2 Spike (S) protein binds to facilitate viral entry, in cord blood derived HSCs/HPCs and in peripheral blood derived immune cell subtypes. ACE2 is expressed in low numbers of immune cells, higher numbers of HPCs, and up to 65% of rigorously defined HSCs. We also examined effects of exposing HSCs/HPCs and immune cells to SARS-CoV-2 S protein ex vivo. HSCs and HPCs expand less effectively and have less functional colony forming capacity when grown with S protein, while peripheral blood monocytes upregulate CD14 expression and show distinct changes in size and granularity. That these effects are induced by recombinant S protein alone and not the infectious viral particle suggests that simple exposure to SARS-CoV-2 may impact HSCs/HPCs and immune cells via S protein interactions with the cells, regardless of whether they can be infected. These data have implications for immune response to SARS-CoV-2 and for HCT. Graphical Abstract • Human HSCs, HPCs, and immune cells express ACE2 on the cell surface, making them potentially susceptible to SARS-CoV-2 infection. • SARS-CoV-2 S protein, which binds to ACE2, induces defects in the colony forming capacity of human HPC and inhibits the expansion of HSC/HPC subpopulations ex vivo. These effects can be at least partially neutralized by treatment with SARS-CoV-2 targeting antibody, recombinant human ACE2, or Angiotensin1-7. • S protein also induces aberrant morphological changes in peripheral blood derived monocytes ex vivo. • Thus, there are many different manners in which SARS-CoV-2 virus may impact the functional hematopoietic system, which has important implications for hematological manifestations of COVID-19 (i.e. thrombocytopenia and lymphopenia), immune response, and hematopoietic stem cell transplant in the era of COVID-19.

Pregnant woman infected by Coronavirus disease (COVID-19) and calcifications of the fetal bowel and gallbladder.

COVID-19 was declared to be a pandemic due to the rapid increase of cases around the world, including the number of pregnant women. Data about vertical transmission of COVID-19 are still limited and controversial: in most cases, although a positive mother, the virus could not be isolated in amniotic fluid, cord blood, breast milk or neonatal throat swab in these patients. No data have been published about possible intrauterine sonographic signs of infection. A pregnant woman was diagnosed with SARS-CoV-2 at 35+5 weeks of gestation and managed conservatively at home. At transabdominal ultrasound at 38+3 weeks, fetal bowel and gallbladder calcifications were noted. CMV and other infectious agents were ruled out; an iterative caesarean section was performed at 38+5 weeks without complications. Placenta resulted negative for SARS-CoV-2; the umbilical cord blood sample was IgG positive and IgM negative as per maternal infection. The baby developed respiratory distress syndrome requiring endotracheal surfactant administration and nasal-CPAP for one day but nasopharyngeal swabs at birth and after 48 hours were SARS-CoV-2 negative. Neonatal abdominal ultrasound showed normal liver, acalculous gallbladder with mild parietal thickening. The baby was discharged in good conditions. Although gallbladder calcifications and echogenic bowel are highly suspicious of viral infection and were thought to be due to the vertical transmission of SARS-CoV-2, these findings were not corroborated by the results of our diagnostic tests; these sonographic findings might represent a false positive of fetal infection in mother affected by COVID-19 since vertical transmission appears to be rare.

Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic.

Importance: Biological data are lacking with respect to risk of vertical transmission and mechanisms of fetoplacental protection in maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective: To quantify SARS-CoV-2 viral load in maternal and neonatal biofluids, transplacental passage of anti-SARS-CoV-2 antibody, and incidence of fetoplacental infection. Design, Setting, and Participants: This cohort study was conducted among pregnant women presenting for care at 3 tertiary care centers in Boston, Massachusetts. Women with reverse transcription-polymerase chain reaction (RT-PCR) results positive for SARS-CoV-2 were recruited from April 2 to June 13, 2020, and follow-up occurred through July 10, 2020. Contemporaneous participants without SARS-CoV-2 infection were enrolled as a convenience sample from pregnant women with RT-PCR results negative for SARS-CoV-2. Exposures: SARS-CoV-2 infection in pregnancy, defined by nasopharyngeal swab RT-PCR. Main Outcomes and Measures: The main outcomes were SARS-CoV-2 viral load in maternal plasma or respiratory fluids and umbilical cord plasma, quantification of anti-SARS-CoV-2 antibodies in maternal and cord plasma, and presence of SARS-CoV-2 RNA in the placenta. Results: Among 127 pregnant women enrolled, 64 with RT-PCR results positive for SARS-CoV-2 (mean [SD] age, 31.6 [5.6] years) and 63 with RT-PCR results negative for SARS-CoV-2 (mean [SD] age, 33.9 [5.4] years) provided samples for analysis. Of women with SARS-CoV-2 infection, 23 (36%) were asymptomatic, 22 (34%) had mild disease, 7 (11%) had moderate disease, 10 (16%) had severe disease, and 2 (3%) had critical disease. In viral load analyses among 107 women, there was no detectable viremia in maternal or cord blood and no evidence of vertical transmission. Among 77 neonates tested in whom SARS-CoV-2 antibodies were quantified in cord blood, 1 had detectable immunoglobuilin M to nucleocapsid. Among 88 placentas tested, SARS-CoV-2 RNA was not detected in any. In antibody analyses among 37 women with SARS-CoV-2 infection, anti-receptor binding domain immunoglobin G was detected in 24 women (65%) and anti-nucleocapsid was detected in 26 women (70%). Mother-to-neonate transfer of anti-SARS-CoV-2 antibodies was significantly lower than transfer of anti-influenza hemagglutinin A antibodies (mean [SD] cord-to-maternal ratio: anti-receptor binding domain immunoglobin G, 0.72 [0.57]; anti-nucleocapsid, 0.74 [0.44]; anti-influenza, 1.44 [0.80]; P < .001). Nonoverlapping placental expression of SARS-CoV-2 receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 was noted. Conclusions and Relevance: In this cohort study, there was no evidence of placental infection or definitive vertical transmission of SARS-CoV-2. Transplacental transfer of anti-SARS-CoV-2 antibodies was inefficient. Lack of viremia and reduced coexpression and colocalization of placental angiotensin-converting enzyme 2 and transmembrane serine protease 2 may serve as protective mechanisms against vertical transmission.

Congenital, Intrapartum and Postnatal Maternal-Fetal-Neonatal SARS-CoV-2 Infections: A Narrative Review.

BACKGROUND: There is inconclusive evidence regarding congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. A narrative review was conducted with the aim of guiding clinicians on the management of pregnant women with respect to congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections and breastfeeding during the COVID-19 pandemic. METHODS: Searches were conducted in Web of Science, PubMed, Scopus, Dialnet, CUIDEN, Scielo, and Virtual Health Library to identify observational, case series, case reports, and randomized controlled trial studies assessing the transmission of SARS-CoV-2 from mother to baby and/or through breastfeeding during the COVID-19 pandemic. RESULTS: A total of 49 studies was included in this review, comprising 329 pregnant women and 331 neonates (two pregnant women delivered twins). The studies were performed in China (n = 26), USA (n = 7), Italy (n = 3), Iran (n = 2), Switzerland (n = 1), Spain (n = 1), Turkey (n = 1), Australia (n = 1), India (n = 1), Germany (n = 1), France (n = 1), Canada (n = 1), Honduras (n = 1), Brazil (n = 1), and Peru (n = 1). Samples from amniotic fluid, umbilical cord blood, placenta, cervical secretion, and breastmilk were collected and analyzed. A total of 15 placental swabs gave positive results for SARS-CoV-2 ribonucleic acid (RNA) on the fetal side of the placenta. SARS-CoV-2 RNA was found in seven breastmilk samples. One umbilical cord sample was positive for SARS-CoV-2. One amniotic fluid sample tested positive for SARS-CoV-2. CONCLUSIONS: This study presents some evidence to support the potential of congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. Mothers should follow recommendations including wearing a facemask and hand washing before and after breastfeeding.