Inflammatory and Immune Responses during SARS-CoV-2 Infection in Vaccinated and Non-Vaccinated Pregnant Women and Their Newborns.

BACKGROUND: Pregnant women are more susceptible to severe disease associated with SARS-CoV-2 infection. We performed a prospective study to analyze the inflammatory and immune profile after SARS-CoV-2 infection occurring in vaccinated or non-vaccinated pregnant women and their newborns. METHODS: Twenty-five pregnant women with SARS-CoV-2 infection were enrolled, and sixteen cord blood samples were obtained at delivery. RESULTS: We observed that IL-1ß, TNF-α, Eotaxin, MIB-1ß, VEGF, IL-15, IL-2, IL-5, IL-9, IL-10 and IL-1ra levels were significantly higher in vaccinated than non-vaccinated mothers. Furthermore, the newborns of the vaccinated mothers produced higher levels of IL-7, IL-5 and IL-12 compared to the newborns of non-vaccinated mothers. Anti-Spike (S) IgG levels were significantly higher in all vaccinated mothers and their newborns compared to the non-vaccinated group. We found that 87.5% of vaccinated women and 66.6% of non-vaccinated women mounted an S-specific T-cell response quantified by ELISpot assay. Moreover, 75.0% of vaccinated mothers and 38.4% of non-vaccinated mothers showed S-specific CD4+ T-cell proliferative response. The T-helper subset response was restricted to CD4+ Th1 in both vaccinated and non-vaccinated women. CONCLUSION: A higher level of cytokines, IgG antibodies and memory T cells was noted in the vaccinated women. Furthermore, the maternal IgG antibody trans-placental transfer occurred more frequently in vaccinated mothers and may protect the newborn.

Adrenal crisis during pregnancy: Case report and obstetric perspective.

Adrenal dysfunction (AD) and, in particular, adrenal crisis are uncommon events in pregnant women, but associated with significant maternal and fetal morbidity and mortality if untreated or undiagnosed. Adrenal crisis may be confused with the common symptoms of pregnancy: the obstetricians should be able to promptly diagnose and treat it in order to avoid the adverse outcomes regarding the mother and the fetus. For this reason, AD must be treated by an expert multidisciplinary team. We presented a case report of a young pregnant woman with adrenal crisis due to tuberculosis, cocaine abuse, and massive bilateral hemorrhage with symptoms of emesis, hypotension, sudden abdominal pain, and leukocytosis. The most common issues of diagnosis and treatment are discussed and analyzed. Finally, we performed a review of the literature regarding adrenal crisis and adrenal insufficiency (AI) in pregnancy in order to clarify the management of these diseases in obstetrics setting.

Impact of SARS-CoV-2 infection during pregnancy and persistence of antibody response.

BACKGROUND: Pregnant women may be at an increased risk of developing severe or critical disease associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection causing severities during pregnancy. We performed a prospective study to describe the impact of SARS-CoV-2 infection on pregnancy outcomes and on the newborn, depending on the severity of the disease. The antibody response and persistence of SARS-CoV-2 anti-Spike (S) IgG, IgA and anti-Nu- cleocapsid (NCP) IgG, was investigated. METHODS: A total of 48 pregnant women with SARS-CoV-2 infection were enrolled, and sequential serum samples from 30 of them were collected until one year after infection. Outcomes of pregnan- cy and newborn parameters were evaluated in comparison with 200 uninfected controls. RESULTS: Asymptomatic infection was observed in 31/48 women (64.5%), mild COVID-19 in 12/48 women (25.0%), while 5/48 women (10.5%) developed pneumonia. Women with pneumonia mount- ed significantly higher levels of anti-S IgG, IgA and anti-NCP IgG between 1 and 3 months after onset of infection compared to asymptomatic women. Anti-S IgG persisted in the majority of women from 6 months to at least one year after infection, especially in those with symptomatic infection and pneumonia, while anti-S IgA and anti-NCP IgG declined earlier. Pregnancy complications and new- born parameters were not significantly different from those observed in uninfected controls. CONCLUSION: Anti-SARS-CoV-2 antibody development and persistence was not impaired in pregnant women, while SARS-CoV-2 infection did not cause major pregnancy or newborn complications in asymptomatic or symptomatic women, nor in women with pneumonia receiving prompt clinical care.

Asymptomatic SARS-CoV-2 infection is not associated with miscarriage in early pregnancy: a retrospective analysis.

The prevalence of SARS-CoV-2 infection during pregnancy is relatively unknown. In this study we report the potential impact of undiagnosed SARS-CoV-2 infection on pregnancy loss in the first half of pregnancy by comparing the prevalence of the infection in a retrospective group of pregnant women with miscarriage (n=62) and a prospective control group with no pregnancy loss in the first trimester (n=218). Of 62 women who had miscarriage, 2 (3.2%) resulted IgM for SARS-CoV-2 negative and IgG seropositive, while of 218 pregnant women, 5 (2.3 %) resulted IgM for negative and IgG seropositive. The SARS-CoV-2 seroprevalence was not significantly different in the two groups of women, therefore excluding a significant role of SARS-CoV-2 infection in pregnancy loss. Therefore, our data show that SARS-CoV-2 infection within the first trimester does not seem to predispose to early pregnancy loss and that the impact of asymptomatic or mildly symptomatic SARS-CoV-2 infection on pregnancy appears limited.

Childbirth Care among SARS-CoV-2 Positive Women in Italy.

The new coronavirus emergency spread to Italy when little was known about the infection's impact on mothers and newborns. This study aims to describe the extent to which clinical practice has protected childbirth physiology and preserved the mother-child bond during the first wave of the pandemic in Italy. A national population-based prospective cohort study was performed enrolling women with confirmed SARS-CoV-2 infection admitted for childbirth to any Italian hospital from 25 February to 31 July 2020. All cases were prospectively notified, and information on peripartum care (mother-newborn separation, skin-to-skin contact, breastfeeding, and rooming-in) and maternal and perinatal outcomes were collected in a structured form and entered in a web-based secure system. The paper describes a cohort of 525 SARS-CoV-2 positive women who gave birth. At hospital admission, 44.8% of the cohort was asymptomatic. At delivery, 51.9% of the mothers had a birth support person in the delivery room; the average caesarean section rate of 33.7% remained stable compared to the national figure. On average, 39.0% of mothers were separated from their newborns at birth, 26.6% practised skin-to-skin, 72.1% roomed in with their babies, and 79.6% of the infants received their mother's milk. The infants separated and not separated from their SARS-CoV-2 positive mothers both had good outcomes. At the beginning of the pandemic, childbirth raised awareness and concern due to limited available evidence and led to "better safe than sorry" care choices. An improvement of the peripartum care indicators was observed over time.

Analysis of SARS-CoV-2 vertical transmission during pregnancy.

The impact of SARS-CoV-2 infection during gestation remains unclear. Here, we analyse the viral genome on maternal and newborns nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk from 31 mothers with SARS-CoV-2 infection. In addition, we also test specific anti-SARS-CoV-2 antibodies and expression of genes involved in inflammatory responses in placentas, and in maternal and umbilical cord plasma. We detect SARS-CoV-2 genome in one umbilical cord blood and in two at-term placentas, in one vaginal mucosa and in one milk specimen. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in one umbilical cord blood and in one milk specimen. Finally, in the three documented cases of vertical transmission, SARS-CoV-2 infection was accompanied by a strong inflammatory response. Together, these data support the hypothesis that in utero SARS-CoV-2 vertical transmission, while low, is possible. These results might help defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.

Concomitant Use of Transcranial Direct Current Stimulation and Computer-Assisted Training for the Rehabilitation of Attention in Traumatic Brain Injured Patients: Behavioral and Neuroimaging Results.

Divided attention (DA), the ability to distribute cognitive resources among two or more simultaneous tasks, may be severely compromised after traumatic brain injury (TBI), resulting in problems with numerous activities involved with daily living. So far, no research has investigated whether the use of non-invasive brain stimulation associated with neuropsychological rehabilitation might contribute to the recovery of such cognitive function. The main purpose of this study was to assess the effectiveness of 10 transcranial direct current stimulation (tDCS) sessions combined with computer-assisted training; it also intended to explore the neural modifications induced by the treatment. Thirty-two patients with severe TBI participated in the study: 16 were part of the experimental group, and 16 part of the control group. The treatment included 20' of tDCS, administered twice a day for 5 days. The electrodes were placed on the dorso-lateral prefrontal cortex. Their location varied across patients and it depended on each participant's specific area of damage. The control group received sham tDCS. After each tDCS session, the patient received computer-assisted cognitive training on DA for 40'. The results showed that the experimental group significantly improved in DA performance between pre- and post-treatment, showing faster reaction times (RTs), and fewer omissions. No improvement was detected between the baseline assessment (i.e., 1 month before treatment) and the pre-training assessment, or within the control group. Functional magnetic resonance imaging (fMRI) data, obtained on the experimental group during a DA task, showed post-treatment lower cerebral activations in the right superior temporal gyrus (BA 42), right and left middle frontal gyrus (BA 6), right postcentral gyrus (BA 3) and left inferior frontal gyrus (BA 9). We interpreted such neural changes as normalization of previously abnormal hyperactivations.

Immunoglobulin E levels in the 1st year of life.

Asthma allergic rhinitis and atopic dermatitis are multifactorial disorders influenced by various familial and environmental factors. The correlation between maternal and fetal immunoglobulin E (IgE) seems to be caused by genetic factors rather than placental transfer. The purpose of this study was to evaluate and quantify the relationship of IgE levels between mothers and their offspring during the 1st year of life. Total serum IgE levels were assessed in 104 healthy pregnant women just before delivery, as well as in 104 newborns in the 1st days of life and then again at 3, 5, 6, 11 and 12 months of age. A serum IgE increase in infants during the 1st year of life is related to maternal serum IgE levels (and may be divided into three classes, according to IgE concentrations of <100, >100, and <260 kU/L), as shown by significant correlation coefficients and regression slopes. Our findings show that IgE levels in infants of mothers who presented serum IgE levels of >100 kU/L exceeded the norm during the 1st year of life, in the absence of overt atopic disease. It seems useful to consider different categories of infants, as a function of their mothers' IgE, to plan a particular follow-up for children in higher risk classes.