SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

Evaluation of Fetal Lung Maturity by Quantitative Analysis (quantusFLM) in Women with Gestational Diabetes Mellitus.

OBJECTIVES: The aim of the present study was to evaluate fetal lung maturity using the noninvasive method of quantitative ultrasound analysis of fetal lung texture (quantusFLM) in women with gestational diabetes mellitus (GDM). METHODS: A total of 96 women at 36-38 weeks of gestation were enrolled. They were classified as follows: 33 GDM cases treated with diet, 30 GDM cases treated with diet plus insulin, and 33 normoglycemic women (control group). A quantitative analysis of lung texture was performed. RESULTS: There were significant differences in the lung maturity results among groups (p = 0.004). These differences were established between the insulin-treated group of patients and both the control (p = 0.006) and diet-only (p = 0.003) groups. While none of the women in the control group or in the diet group had a high risk of immaturity, 16.7% of those treated with insulin (5/30) did (p = 0.003). There was no statistically significant correlation between HbA1c and the result of the test. CONCLUSIONS: Quantitative ultrasound study of fetal lung texture suggests that a significant percentage of pregnant women with GDM treated with insulin had fetal lung immaturity in the late preterm to early term.

Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

AIM: Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. MATERIALS AND METHODS: A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. RESULTS: The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). CONCLUSIONS: Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

Newborn feeding behaviour depressed by intrapartum oxytocin: a pilot study.

AIM: To investigate the effect intrapartum oxytocin administration can have on Primitive Neonatal Reflexes. The secondary objective was to observe the influence of intrapartum oxytocin may have on breastfeeding. METHODS: Twenty healthy primiparae with a single gestation at term were included. To assess Primitive Neonatal Reflexes, video film was taken during an experimental situation designed to elicit Primitive Neonatal Reflexes. Three independent observers blinded to the oxytocin dose that had been administered coded the Primitive Neonatal Reflexes. Data regarding breastfeeding were collected by telephone at 3 months. RESULTS: Medium oxytocin dose was 1931.9 ± 1754.4 mUI. A Kappa index >0.75 was obtained for four Primitive Neonatal Reflexes: swallow, jaw jerk, suck and gazing. A negative association was found between oxytocin dose and sucking (p = 0.03). At 3 months of life, women exclusively breastfeeding (63.1%) had received a significantly lower average dose of oxytocin than those not exclusively breastfeeding (36.8%) (p = 0.04). CONCLUSION: In this pilot study, intrapartum exogenous oxytocin seems to disturb sucking and breastfeeding duration. Further studies are required to confirm these results and to ascertain whether there could be other effects of intrapartum oxytocin on newborn behaviour.

Oxytocin and autism: a hypothesis to research. Can perinatal oxitocinergic manipulation facilitate autism?

The study of the neurohormonal and behavioral processes and neural mechanisms involved in the development of attachment between the infant and the mother has received increased attention over the last years. Oxytocin has been shown to play a central role in the regulation of affiliate social behavior, including sexual behavior, mother infant bonding and social memory and recognition. Following normal physiological vaginal birth highest levels plasmatic endogenous oxytocin are achieved, which has been related to the presence of a sensitive period which seems to facilitate bonding and initial mother and newborn attachment. Perinatal manipulation of peptidic hormones like oxytocin can have life long lasting effects on social and sexual behaviors in animal models. Disregulation of oxytocinergic system has been observed in individuals with autistic disorders. A review of the possible effects of oxytocinergic perinatal manipulation in human newborns is discussed in the present review article. The hypothesis of the possible effect of perinatal oxytocin manipulation on the ethiology of autism is discussed.