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The relationship between the incidence of COVID-19 in pregnant women who have had a coronavirus infection at different gestational ages and the health status of paired neonates is of great interest. However, no sufficient convincing data fully reflecting features of subsequent neonatal period, the state of the immune system in this category of children, affecting characteristics of postnatal period have been accumulated. Based on this, it underlies the relevance of the current study aimed at investigating parameters of clinical and immunological state of neonatal health after paired mothers recovered from COVID-19 at different gestational ages. The prospective study included 131 women and 132 children. The main group consisted of women (n = 61) who had COVID-19 during pregnancy and paired newborns (n = 62) at gestational age (GA) of 3741 weeks, the comparison group women without laboratory-confirmed COVID-19 during pregnancy (n = 70) and paired newborns (n = 70) of similar gestational age. While analyzing the anamnesis of the patients, no significant differences in somatic and obstetric-gynecological diseases were found. Analyzing course of pregnancy revealed that low molecular weight heparins were significantly more often applied in the main group. The term and frequency of delivery by caesarean section in pregnant women in the main group did not significant differ from that of the control group. No significant difference in the frequency of causes accounting for the severity of the condition of neonates in paired mothers with COVID-19 at different trimester of gestation was found. Investigating lymphocyte subset composition, neutrophil phagocytic activity, and IgG class antibodies specific to SARS-CoV-2 was carried out. It was found that lymphocyte subset profile in newborns from paired mothers with COVID-19 at different trimesters of gestation differed only in the level of NK cells (CD56+) in children born to mothers recovered from COVID-19 in the first trimester. In this study, in general, no severe perinatal outcomes in newborns from paired mothers with COVID-19 during pregnancy were documented. No cases of moderate or severe maternal COVID-19 were observed. Therefore, further prospective studies are needed to assess an impact of COVID-19 severity on maternal and fetal birth outcomes and clarify optimal management of pregnant women in such cases.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.

The content of eight different cytokines, cell-free DNA (cfDNA) and cell-free fetal DNA (cffDNA) in women's plasma during preterm birth (PB) was studied. The purpose of this study was to identify the relationships between the investigated factors and determine their prognostic significance.Venous blood samples were collected from 45 women with PB and 35 women with full-term labor at 22-31 and 32-36 weeks of gestation, as well as from 17 women during labor at 39-40 weeks of gestation. The concentration of IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-γ and TNF-α cytokines in peripheral blood plasma was measured by multiplex method. The level of cfDNA and cffDNA was evaluated using PCR analysis.It was found that, the level of IL-6, IL-8 and cfDNA in the blood was significantly increased in women with PB at 22-31 weeks of gestation (p = 0.044, p = 0.001, p 0.001) and 32-36 weeks of gestation (p = 0.025, p = 0.001, p = 0.002) compared to women with physiological pregnancy at the same terms. The level of cffDNA (p = 0.014) was significantly increased in women with PB at 32-36 weeks of gestation. The IL-8 content had a significant correlation with the cfDNA level in women with PB at all stages of labor and with the cffDNA level in the group who gave birth at 32-36 weeks of gestation. There was no correlation between IL-8, cfDNA and cffDNA, but there was consistency with other cytokines at all studied terms and during delivery in the term-delivery group.The results of the study suggest that cfDNA is a potential marker of PB and show that the aberrant relationship between cfDNA and IL-8 may be important in the genesis of PB.

The breastfeeding of infants by mothers who are infected with SARS-CoV-2 has become a dramatic healthcare problem. The WHO recommends that infected women should not abandon breastfeeding; however, there is still the risk of contact transmission. Convalescent donor milk may provide a defense against the aforementioned issue and can eliminate the consequences of artificial feeding. Therefore, it is vital to characterize the epitope-specific immunological landscape of human milk from women who recovered from COVID-19. We carried out a comprehensive ELISA-based analysis of blood serum and human milk from maternity patients who had recovered from COVID-19 at different trimesters of pregnancy. It was found that patients predominantly contained SARS-CoV-2 N-protein-specific immunoglobulins and had manifested the antibodies for all the antigens tested in a protein-specific and time-dependent manner. Women who recovered from COVID-19 at trimester I–II showed a noticeable decrease in the number of milk samples with sIgA specific to the N-protein, linear NTD, and RBD-SD1 epitopes, and showed an increase in samples with RBD conformation-dependent sIgA. S-antigens were found to solely induce a sIgA1 response, whereas N-protein sIgA1 and sIgA2 subclasses were involved in 100% and 33% of cases. Overall, the antibody immunological landscape of convalescent donor milk suggests that it may be a potential defense agent against COVID-19 for infants, conferring them with a passive immunity.

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17&alpha, OH progesterone (17&alpha, OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4&ndash, 13.8) vs. 3.7 (2.5&ndash, 4.7) IU/L, p &lt, 0.0001), LH/FSH (1.6 (1.0&ndash, 2.3) vs. 0.7 (0.5&ndash, 1.1), 0.0001), 17&alpha, &ndash, OHP (4.1 (3.2&ndash, 5.1) vs. 3.4 (2.7&ndash, 3.8) nmol/L, p = 0.0071), cortisol (464.0 &plusmn, 147.6 vs. 284.0 &plusmn, 129.7 nmol/L, 0.0001), prolactin (266.0 (175.0&ndash, 405.0) vs. 189.0 (142.0&ndash, 269.0) mIU/L, p = 0.0141), T (1.9 (1.2&ndash, 2.5) vs. 0.8 (0.7&ndash, 1.1) nmol/L, 0.0001), androstenedione (15.8 (11.6&ndash, 23.2) vs. 8.3 (6.5&ndash, 10.8) ng/mL, 0.0001), AMH (9.5 (7.5&ndash, 14.9) vs. 5.8 (3.8&ndash, 6.9) ng/mL, 0.0001), FAI (5.5 (2.8&ndash, 7.0) vs. 1.6 (1.1&ndash, 2.3), 0.0001), SHBG (37.0 (24.7&ndash, 55.5) vs. 52.9 (39.0&ndash, 67.6) nmol/L, p = 0.0136), DHEAS (6.8 &plusmn, 3.2 vs. 5.1 &plusmn, 1.5 &mu, mol/L, p = 0.0039), and leptin (38.7 &plusmn, 27.1 vs. 23.7 &plusmn, 14.0 ng/mL, p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level &gt, 7.20 ng/mL, FAI &gt, 2.75, androstenedione &gt, 11.45 ng/mL, total T &gt, 1.15 nmol/L, LH/FSH ratio &gt, 1.23, and the volume of each ovary &gt, 10.70 cm3 (for each criterion sensitivity &ge, 75.0&ndash, 93.0%, specificity &ge, 83.0&ndash, 93.0%). The diagnostic accuracy of PCOS determination was 90.2&ndash, 91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 &minus, (1.73 &times, AMH) &minus, (0.12 &times, Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.

Relevance: Mitochondrial dysfunction and systemic inflammation are believed to play pivotal role in the pathogenesis of polycystic ovary syndrome (PCOS) and related complications of metabolic disorders in adult patients. Though such researches are limited or almost absent in adolescents. The aim of the study is to evaluate the impact of mitochondrial dysfunction and systemic inflammation on PCOS pathogenesis during adolescence with regard to body mass index and insulin resistance. Design: a case-control study. Methods: The study included 95 adolescent girls (15 to 17 years old inclusive) diagnosed with PCOS based on the Rotterdam criteria. The control group consisted of 30 healthy girls of the same age with a regular menstrual cycle. All participants were subjected to a full clinical and instrumental examination, as well as an assessment of the levels of leptin, C-reactive protein (CRP), and malondialdehyde (MDA) as oxidative stress marker. Serum levels of IL-6, IL-10, IL-18, TNF-&alpha, and plasma concentrations of macrophage migration inhibitory factor (MIF), sFas, and sFasL were determined. Patients with PCOS were divided into groups according to the presence of metabolic disorders (MD) (impaired glucose tolerance and/or over insulin resistance) and normal weight or excessive weight (NW or OW). Results: Patients with PCOS of NW in the absence of metabolic disorders (MD&minus, /NW) had a lower concentration of MDA and a higher level of IL-10 compared to healthy girls (p &lt, 0.05). The group (MD&minus, /NW) was characterized with lower levels of CRP, leptin, MDA, and higher levels of sFasL, when compared to OW patients with PCOS in the absence of metabolic disorders (MD&minus, /OW) (p &lt, 0.05). Overweight adolescent girls with PCOS and metabolic disorders (MD+/OW) showed higher CRP, leptin, and a two-fold increase in IL-6 and IL-18 concentrations compared to the control group of healthy girls (p &lt, 0.05 for all parameters). The group (MD+/OW) was also characterized with higher levels of CRP, leptin, MDA, IL-18, MIF (p &lt, 0.05), when compared to overweight patients with PCOS in the absence of metabolic disorders (MD&minus, /NW). In comparison with the MD&minus, /OW group, the obese insulin resistant girls with PCOS (MD+/OW) had a highera level of IL-18 (p &lt, 0.05). Moreover, the MD+/OW girls demonstrated a significant increase in CRP, MDA and IL-18 levels when compared to the MD+/NW group (p &lt, 0.05). OW girls with PCOS without MD (MD&minus, /OW) had lower concentrations of sFasL compared to healthy girls (p &lt, 0.05), and higher levels of MDA compared to MD+/NW (p &lt, 0.05). Adolescent girls of NW with PCOS and with MD (MD+/NW) had lower levels of MDA compared to the control group of healthy girls (p &lt, 0.05). These data are confirmed by a correlation analysis and two-factor ANOVA test. Conclusions: Lean girls with PCOS demonstrate the protective mechanism of decrease in oxidative stress mediated by the activation of antioxidant defense, reduction of lipid peroxidation and systemic inflammation. Excessive weight and metabolic disorders in adolescents with PCOS are the most significant factors in reducing the capacity of antioxidant systems, activation of oxidative stress, mitochondrial dysfunction, and systemic inflammation.