Seroprevalence of SARS-CoV-2 immunoglobulins in pregnant women and neonatal cord blood from a highly impacted region.

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.

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.

High incidence of Zika virus infection detected in plasma and cervical cytology specimens from pregnant women in Guayaquil, Ecuador.

Zika virus (ZIKV) infection during pregnancy has been linked to severe birth defects, and the epidemiologic situation of the ZIKV epidemic in Ecuador is poorly understood. Guayaquil, Ecuador, has a tropical climate and experiences frequent outbreaks of dengue and chikungunya virus, and in December 2015, ZIKV was identified. Given the well-documented effects of ZIKV in pregnancy, including microcephaly, we tested for the presence of ZIKV in both plasma and cervical cytology of pregnant women. We report the identification of a population of pregnant women with a high incidence of ZIKV infection detected in the plasma and lower reproductive tract. A case-control study was performed to determine the incidence of ZIKV infection among low-income, pregnant women at risk for preterm delivery compared to matched controls. Plasma and cervical cytology specimens were tested for ZIKV by rRT-PCR. Fifty-nine pregnant women were enrolled. The incidence of ZIKV was 54% (32/59) overall: 18/31 (58.1%) in cases and 14/28 (50.0%) in controls. ZIKV detection in plasma and cervical cytology specimens demonstrated good agreement. Overall, outcomes for neonates born to ZIKV-positive and ZIKV-negative mothers were similar. However, two neonates were born with microcephaly to case mothers who were ZIKV positive. We report a high incidence of ZIKV infection (54%) in a distinctive population in Guayaquil, Ecuador. We identify ZIKV in cervical samples that correlates with ZIKV in the plasma. These data raise concerns regarding the breadth of the ZIKV epidemic in Ecuador and demonstrate the utility of cervical cytology specimens for ZIKV testing.

Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells.

PROBLEM The specialized regulatory T-cells (Treg) population, essential for maternal tolerance of the fetus, performs its suppressive actions in the critical peri-implantation phase of pregnancy. In the present work, we investigated whether trophoblast cells are able to induce Treg recruitment, differentiation, and whether these mechanisms are modified by a bacterial or viral infection. METHOD OF STUDY Human T-regulatory cells were differentiated from naïve CD45RA(+) CCR7(+) cells obtained from peripheral blood mononuclear cells cultured with IL-2 and TGFß over 5 days. Induction of iTregs (CD4(+) Foxp3(+) cells) was evaluated using low serum conditioned media (LSCM), obtained from two first trimester trophoblast cell lines, Swan-71 and HTR8. Coculture experiments were carried out using transwell assays where trophoblast cells were in the absence or presence of PGN, LPS, or Poly [I:C]. Cytokine production was measured by multiplex analysis. RESULTS Trophoblast cells constitutively secrete high levels of TGFß and induced a significant increase of Foxp3 expression accompanied by a specific T-reg cytokine profile. Moreover, trophoblast cells were able to recruit iTregs in a specific manner. CONCLUSION We demonstrate that trophoblast cells have an active role on the recruitment and differentiation of iTregs, therefore, contributing to the process of immune regulation at the placental-maternal interface.

A potential tolerogenic immune mechanism in a trophoblast cell line through the activation of chemokine-induced T cell death and regulatory T cell modulation.

BACKGROUND: Successful implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by Th2. Regulated upon activation, normal T cell expressed and secreted (RANTES) promotes a Th1 response and is implicated as a physiologic tolerogenic factor; therefore, we studied its potential role in the trophoblast-maternal leukocyte dialog. METHODS: We performed co-cultures of immortalized trophoblast cell line (Swan 71) and peripheral blood mononuclear cells (PBMCs) from fertile women (n = 23) or with recurrent spontaneous abortions (n = 18, RSA). After 24 and 48 h, supernatant and cells were analyzed by enzyme-linked immunosorbent assay, fluorescence-activated cell sorting, Western blot and apoptosis assay. To investigate the physiological effects at peripheral level, we co-cultured maternal and paternal PBMCs with conditioned media from Swan cells and progesterone. RESULTS: Following interaction of maternal PBMCs and trophoblast cells, RANTES production increased (P < 0.05) and was accompanied by low levels of interferon gamma, interleukin-12 p70 and high levels of tumor necrosis factor-alpha, nitrites and leukemia-inhibitory factor. RANTES production resulted in elevated apoptosis of potentially deleterious maternal CD3+ lymphocytes, accompanied by a decrease in the proliferative maternal response. During fetal-maternal dialog, the anti-RANTES antibody significantly reduced the frequency of CD4+CD25+Foxp3+ cells (P < 0.05) and was associated with trophoblast cell survival. However, co-cultures of Swan cells and RSA-PBMCs displayed a differential RANTES kinetics, lower levels of regulatory T cells (Tregs) and CD3+annexin-V+cells, accompanied by higher levels of apoptotic trophoblast cells. CONCLUSIONS: RANTES promotes an adequate pro-implantatory microenvironment that influences trophoblast cell survival and modulates the balance of maternal Treg/T effector lymphocytes in favor of maternal tolerance.