SARS-CoV-2 Infection in Pregnant Women: Neuroimmune-Endocrine Changes at the Maternal-Fetal Interface.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has devastating effects on the population worldwide. Given this scenario, the extent of the impact of the disease on more vulnerable individuals, such as pregnant women, is of great concern. Although pregnancy may be a risk factor in respiratory virus infections, there are no considerable differences regarding COVID-19 severity observed between pregnant and nonpregnant women. In these circumstances, an emergent concern is the possibility of neurodevelopmental and neuropsychiatric harm for the offspring of infected mothers. Currently, there is no stronger evidence indicating vertical transmission of SARS-CoV-2; however, the exacerbated inflammatory response observed in the disease could lead to several impairments in the offspring's brain. Furthermore, in the face of historical knowledge on possible long-term consequences for the progeny's brain after infection by viruses, we must consider that this might be another deleterious facet of COVID-19. In light of neuroimmune interactions at the maternal-fetal interface, we review here the possible harmful outcomes to the offspring brains of mothers infected by SARS-CoV-2.

Effect of maternal immunization against pertussis in Medellin and the metropolitan area, Colombia, 2016-2017.

BACKGROUND: In 2013, pertussis immunization (Tdap) for pregnant women was implemented in Colombia to protect newborns in response to increased pertussis incidence. OBJECTIVE: To assess the effect of Tdap maternal immunization on the concentration of mother/umbilical cord antibodies and the occurrence of pertussis in infants during their first six months of life. METHODS: A cohort study in eight randomly selected hospitals in Medellin and metropolitan area of Antioquia, Colombia was conducted in 2015-2016. IgG PT antibody levels in paired maternal and umbilical cord sera were measured from 805 mothers immunized recruited during labor and 200 mothers recruited during the prenatal care before immunization and followed until delivery. Antibodies were analyzed by commercial ELISA kits. 896 infants were followed to detect acute respiratory infections and paroxysms of coughing, inspiratory whoop, apnea, cyanosis or post-tussive vomiting. For laboratory confirmation, B. pertussis- specific real time PCR was performed. RESULTS: We observed a high prevalence of titers >100 IU/mL (mother: 18.40% [95% CI 16-21%]; umbilical cord: 23.1% [95% CI 19.2-27.4%]), positive correlation of umbilical cord and maternal antibodies, higher antibody concentration in vaccinated than in non-vaccinated mothers and significant difference in antibody levels before and after vaccination (Wilcoxon test p = 0.000). The trans placental transport ratio was higher if the mother was vaccinated between 26 and 30 weeks of pregnancy and maximum eight weeks before delivery. Two cases of pertussis were confirmed in infants (incidence of 1.99 per 1000). CONCLUSION: The expected effect of Tdap maternal vaccination against pertussis was observed.

Herpes simplex virus type 2 IgG antibodies in sera of umbilical cord as a proxy for placental infection in asymptomatic pregnant women.

PROBLEM: Herpes simplex virus type 2 (HSV-2) infection is one of the most prevalent diseases worldwide and is mainly sexually transmitted. When infecting pregnant women, HSV-2 is able to infect the placenta, can reach the fetus, and may affect the fetal development. We sought to determine the prevalence of HSV-2 infection and reactivation in asymptomatic pregnant women, the correlation between IgG in the maternal circulation and cord blood, and the correlation between circulating IgG, placental, and newborn infection (blood cord). METHOD OF STUDY: Serum samples and placental tissues from pregnant women and umbilical cord blood samples from their newborns were collected. Anti-HSV-2 antibodies were identified by ELISA, and HSV-2 DNA was detected by nested PCR. RESULTS: The seropositivity of IgG in pregnant women was 29.7% and IgM was detected in 1 woman (0.5%). In the umbilical cord of newborns, 33.1% were IgG-positive and IgM was detected in 2 samples (1.5%). A positive correlation between HSV-2 IgG titers in serum from pregnant women and cord blood samples was found (r = .36, P = .001). A difference between the positive and negative placental groups (maternal side) was found in titers of IgG in sera of umbilical cord, which were significantly higher in the positive placental group (P = .004). CONCLUSION: We describe for the first time that newborns from mothers with HSV-2 placental infection have higher IgG titers in sera of umbilical cord, suggesting IgGs antibodies can be indicative of placental viral infection in asymptomatic women.

Frequency of Toxocara spp. antibodies in umbilical cords of newborns attended atthe University Hospital in Southern Brazil and factors associated with infection.

Toxocariasis is a neglected and geographically widespread parasitic disease. The detection of specific antibodies associated with this disease is required to confirm its clinical diagnosis and to aid in prevention. Although helminth infection during pregnancy can promote foetal immune responses with long-term effects, specific information regarding the risk of Toxocara spp. infection to the human foetus during pregnancy is lacking. Therefore, the present study aimed to investigate the frequency of antibodies against Toxocara spp. in umbilical cord serum samples to determine the neonatal risk factors associated with Toxocara spp. infection. A cross-sectional study of the frequency of specific antibodies against Toxocara spp. was performed on umbilical cord samples of 280 neonates. A cord blood sample was obtained from each newborn after parturition, and serum samples were examined by enzyme-linked immunoassay. Epidemiological data were obtained through a questionnaire regarding obstetric history (abortion history, premature birthhistory, and pregnancy and birth numbers), general aspects (animal contact anddiet) and socio-economic factors. The frequency of anti-Toxocara spp. IgG antibodies in the umbilical cords of neonates was 20% in serum pre-adsorbed with Ascaris spp. antigen. Family income and dog ownership were considered risk factors associated with infection. No association was found between reproductive disorders and Toxocara seropositivity. The 20% frequency rate of anti-Toxocara spp. IgG antibodies in sera from umbilical cords of newborns can be related to IgG binding at the maternal-foetal interface, requiring greater care during pregnancy. Anti-Toxocara IgM and IgE antibodies no were found in umbilical cord serum samples, indicating that no vertical transmission of these parasites occurred in this population. Studies regarding antibodies against Toxocara spp. in umbilical cord sera are important for determining neonatal exposure to these parasites.

Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization

OBJECTIVE: To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery. METHODS: We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-). RESULTS: Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups. CONCLUSIONS: Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

Stirred tank bioreactor culture combined with serum-/xenogeneic-free culture medium enables an efficient expansion of umbilical cord-derived mesenchymal stem/stromal cells.

Mesenchymal stem/stromal cells (MSC) are being widely explored as promising candidates for cell-based therapies. Among the different human MSC origins exploited, umbilical cord represents an attractive and readily available source of MSC that involves a non-invasive collection procedure. In order to achieve relevant cell numbers of human MSC for clinical applications, it is crucial to develop scalable culture systems that allow bioprocess control and monitoring, combined with the use of serum/xenogeneic (xeno)-free culture media. In the present study, we firstly established a spinner flask culture system combining gelatin-based Cultispher(®) S microcarriers and xeno-free culture medium for the expansion of umbilical cord matrix (UCM)-derived MSC. This system enabled the production of 2.4 (±1.1) x10(5) cells/mL (n = 4) after 5 days of culture, corresponding to a 5.3 (±1.6)-fold increase in cell number. The established protocol was then implemented in a stirred-tank bioreactor (800 mL working volume) (n = 3) yielding 115 million cells after 4 days. Upon expansion under stirred conditions, cells retained their differentiation ability and immunomodulatory potential. The development of a scalable microcarrier-based stirred culture system, using xeno-free culture medium that suits the intrinsic features of UCM-derived MSC represents an important step towards a GMP compliant large-scale production platform for these promising cell therapy candidates.

Passive acquisition of anti-Staphylococcus aureus antibodies by newborns via transplacental transfer and breastfeeding, regardless of maternal colonization.

OBJECTIVE:: To investigate the transmission of anti-Staphylococcus aureus (Sa) IgG, IgG1 and IgG2 via placental transfer and the transfer of IgA via the colostrum according to maternal Sa carrier status at delivery. METHODS:: We evaluated anti-Sa IgG, IgG1 and IgG2 in maternal and cord sera and IgA in colostrum from a case (n=49, Sa+) and a control group (n=98, Sa-). RESULTS:: Of the 250 parturients analyzed for this study, 49 were nasally colonized with S. aureus (prevalence of 19.6%). Ninety-eight non-colonized subjects were selected for the control group. The anti-Sa IgG, IgG1 and IgG2 levels and the IgG avidity indexes in the maternal and cord sera did not differ between the groups, with a low transfer ratio of anti-Sa IgG to the newborns in both groups. The anti-Sa IgG2 titers were significantly higher than the IgG1 titers in the maternal and cord sera. Inversely, the transfer ratios were higher for anti-Sa IgG1 compared with IgG2; however, no differences between the groups were detected. The Sa-specific IgA levels and avidity indexes in the colostrum were equivalent between groups. CONCLUSIONS:: Maternal Sa nasal colonization at delivery is not associated with higher antibody levels in the mother or newborns. The high titers of anti-Sa IgG2 found in the cord serum indicate a greater reactivity with non-protein antigens, which may further contribute to the susceptibility to staphylococcal infections at birth. The presence of IgA in the colostrum with avidity to S. aureus reinforces the importance of breastfeeding shortly after birth.

Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson's disease.

Microglial activation in the substantia nigra (SN) is a ubiquitous feature in PD which could mediate toxic effects. Human mesenchymal stromal cells (hMSCs) possess immunomodulatory properties. We evaluated whether the transplantation of hMSCs obtained from umbilical cord had a neuroprotective effect in a not-immunosuppressed rat Parkinson's disease (PD) model. Rats receiving hMSCs in the SN displayed significant preservation in the number of dopaminergic neurons in the SN at 21 days after lesion and an improved performance in behavioral tests compared to control rats. However, no differences in any inflammatory parameter tested were found. These results suggest that grafted hMSCs exert neuroprotection but not neuromodulatory effects on degenerating dopaminergic neurons.

Determining IgA and IgG antigliadin, IgA antitransglutaminase, and antiendomysial antibodies in monkey esophagus and in umbilical cord for diagnosis of celiac disease in developing countries.

OBJECTIVES: To assess the efficiency of determining IgA and IgG antigliadin antibodies (IgA- and IgG-AGA, respectively), antitransglutaminase (TgA), and anti-endomysial antibodies (AEA) in human umbilical cord (CO) and monkey esophagus for diagnosis of celiac disease; to determine the correlation between serological markers and celiac disease. PATIENTS AND METHODS: A total of 400 patients were divided in 3 groups: group 1 with 37 patients with celiac disease, group 2 with 208 patients with no enteropathies, and group 3 with 155 patients with other enteropathies. IgA-AGA, IgG-AGA, and TgA were assessed using enzyme-linked immunosorbent assay, whereas AEA was evaluated by indirect immunofluorescence. RESULTS: Sensitivity and specificity of IgA-AGA were 81.1% and 95.2%, of IgG-AGA 89.2% and 95.2%, of TgA 83.9% and 96.8%, of AEA-CO 87.9% and 100%, and of AEA of monkey esophagus 88.6% and 100%, respectively. Positive predictive values were 75.0%, 76.7%, 83.9%, and 100%. Negative predictive values were 96.6%, 98.0%, 96.8%, and 97.7% for IgA-AGA, IgG-AGA, TgA, and AEA, respectively. Multivariate analysis showed a strong association between AEA-CO and celiac disease and a good correlation with other markers (TgA, IgA-AGA, and IgG-AGA). CONCLUSIONS: TgA has been recommended for screening patients with celiac disease. Considering the similar sensitivity and specificity of IgA-AGA and TgA and their correlations in the multivariate analysis, both are applicable for this purpose. However, because TgA tests are highly costly and celiac disease is associated with IgA deficiency, the determination of IgA-AGA and IgG-AGA, followed by AEA-CO, is suitable for screening in developing countries, provided a cutoff point for these examinations is established. The results of antiendomysial antibodies in umbilical cord overlapped those in monkey esophagus. Therefore, umbilical cord should be used as a substrate instead of specimens from endangered species.

Anionic sites, fucose residues and class I human leukocyte antigen fate during interaction of Toxoplasma gondii with endothelial cells.

Toxoplasma gondii invades and proliferates in human umbilical vein endothelial cells where it resides in a parasitophorous vacuole. In order to analyze which components of the endothelial cell plasma membrane are internalized and become part of the parasitophorous vacuole membrane, the culture of endothelial cells was labeled with cationized ferritin or UEA I lectin or anti Class I human leukocyte antigen (HLA) before or after infection with T. gondii. The results showed no cationized ferritin and UEA I lectin in any parasitophorous vacuole membrane, however, the Class I HLA molecule labeling was observed in some endocytic vacuoles containing parasite until 1 h of interaction with T. gondii. After 24 h parasite-host cell interaction, the labeling was absent on the vacuolar membrane, but presents only in small vesicles near parasitophorous vacuole. These results suggest the anionic site and fucose residues are excluded at the time of parasitophorous vacuole formation while Class I HLA molecules are present only on a minority of Toxoplasma-containing vacuoles.

Valor predictivo de la IgE en el recién nacido / Predictive value of the IgE in newborn

Para determinar la relación de los títulos de IgE y el desarrollo de alergia en la lactancia se cuantificaron los niveles de esta inmunoglobulina en la sangre del cordón umbilical en recién nacidos de término, eutróficos y sanos nacidos en forma consecutiva en un periodo de dos meses, efectuándose seguimiento durante seis meses. Se incluyó un total de 74 recién nacidos. La media de la IgE fue de 0.08 UI/ml con desviación estándar de 0.15. Durante el seguimiento sólo dos niños desarrollaron alergia, lo que determinó un valor predictivo negativo para IgE de 94 por ciento. Nuestros resultados concuerdan con los de otros autores respecto al alto valor predictivo negativo de los niveles nominales o bajos de IgE en la sangre del cordón umbilical y el desarrollo de alergia, concluyéndose que su determinación debería limitarse a los niños con antecedente familiar de atopia para mejorar la capacidad de predicción de esta enfermedad

Frecuencia de anticuerpos séricos contra Pneumocystis carinii en un grupo de mujeres embarazadas sanas y sus productos / Frequency of serum antibodies againts Pneumocystis carinii in a group of health pregnant women and their infants

Para determinar la frecuencia con la que se encuentran anticuerpos contra Pneumocystis carinii en un grupo de 58 mujeres embarazadas sanas, y la frecuencia con la que transfieren estos anticuerpos al producto, se utilizaron muestras de suero tomadas de la madre al momento del parto y del cordón umbilical para búsqueda de anticuerpos por la técnica de Western blot (inmunotransferencia). Se utilizó como fuente de antígeno P. carinii derivado de rata inmunosuprimida. En 28 (48 por ciento) sueros se identificó la presencia de anticuerpos contra P. carinii; existió prueba de transferencia en 21 (75 por ciento) de las muestras tomadas del cordón umbilical. El antígeno más reconocido estuvo entre 45-55 kDa. En 20 por ciento de las muestras maternas, se encontró reconocimiento al antígeno de 95 kDa, a diferencia de las muestras tomadas del cordón umbilical, en las cuales no se identificó respuesta contra este antígeno, que suponemos puede der detectado en la primoinfección natural

Concentración de IgE en sangre de cordón umbilical en recién nacidos sanos / Concentration of IgE in blood of the umbilical cord in newborn

Las concentraciones séricas de IgE se modifican por factores como edad, raza, condiciones ambientales y estado de salud. Se estudiaron 113 niños recién nacidos de 38 a 42 semanas de gestación, clínicamente sanos, a los que se les extrajo sangre del cordón umbilical y se les midió la concentración de IgE por el método de ELISA. Se obtuvieron los siguientes resultados: 85 por ciento de los niños recién nacidos tenían concentraciones de IgE de 0.5 UI/ml a 4.0 UI/ml. No se observaron diferencias estadísticamente significativas respecto a la edad gestacional o el sexo. Las concentraciones séricas de IgE observadas en estos pacientes fueron un poco mayores que las informadas en otros grupos estudiados. Esos resultados pueden considerarse para el diagnóstico de enfermedades alérgicas en recién nacidos e identificación de factores de riesgo

Niveles de IgM en sangre del cordón umbilical / Levels of IgM in the umbilical cord

Se determinaron los niveles de IgM en el cordón umbilical de 42 niños, 25 sanos y 17 cuyas madres tenían de patología durante el embarazo. Dos muestras de los casos con historia de patología resultaron elevadas para un 11.8%

Development of the capacity to produce specific antibody to an ingested food antigen in the premature infant.

Thirteen premature infants were given bovine serum albumin, a cow milk protein, by addition to their formula. Serum antibodies to BSA developed in three infants 36-38 weeks' gestation, confirming that exposure to the antigen in the gastrointestinal tract will immunize infants born after 36 or more weeks' gestation. Serum antibodies to BSA, however, were detected in only one of two infants of 35 weeks' and in none of eight infants of 30-34 weeks' gestation. The results show that the capacity to make specific antibodies to BSA develops around 35-36 weeks' gestation, despite the prior appearance of organized lymphoid tissue and independent of antigen exposure.