EFFECT OF COVID-19 VACCINATION ON THE IMMUNE STATUS AND AUTOANTIBODY PROFILE IN WOMEN OF REPRODUCTIVE AGE.

In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women's reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective(s): to evaluate the effect of the "Gam-COVID-Vac" on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age. The prospective study included 120 women who were vaccinated against COVID-19 with the "Gam-COVID-Vac". The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies. The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response. Vaccination with "Gam-COVID-Vac" is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response. Copyright © 2022, SPb RAACI.

EFFECT OF COVID-19 VACCINATION ON THE IMMUNE STATUS AND AUTOANTIBODY PROFILE IN WOMEN OF REPRODUCTIVE AGE

In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women's reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the "Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age. The prospective study included 120 women who were vaccinated against COVID-19 with the "Gam-COVID-Vac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies. The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response. Vaccination with "Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response. © 2022, SPb RAACI.

Mild or Moderate COVID-19 during Pregnancy Does Not Affect the Content of CD34+ Hematopoietic Stem Cells in Umbilical Cord Blood of Newborns.

The study included umbilical cord blood samples (n=64) intended for cryogenic storage of hematopoietic stem cells and obtained from patients with a history of mild and moderate forms of COVID-19 during pregnancy. The control group was composed of samples (n=746) obtained from healthy women in labor. A comparative analysis of the volume of cord blood collected, the total leukocyte count, the relative and absolute content of cells with the CD34+/CD45+ phenotype revealed no significant differences between the groups.

EFFECTS OF COVID-19 VECTOR VACCINE ON AUTOANTIBODY PROFILE IN REPRODUCTIVE AGE WOMEN

Autoimmune mechanisms have been implicated in the negative effects of vaccines on female reproductive health. This study evaluates the endogenous levels of self-reactive antibodies and ovarian reserve-associated hormones before and after immunization with the domestically developed Gam-COVID-Vac combined vector vaccine to check for possible reproductive sequelae. The prospective study enrolled 120 women aged 18–49, subject to vaccination with Gam-COVID-Vac. Ovarian reserve was assessed prior to vaccination and 90 days after the first component injection. Profiles of specific antibodies to self-antigens, including phospholipids, nuclear antigens, FSH, progesterone, and also thyroid, ovarian, trophoblast, and zona pellucida antigens, were assessed at the same time points by enzyme immunoassay. Overall, the vaccination had no effect on the levels of ovarian reserve-associated hormones and autoantibodies, apart from a transient increase in positivity for antiphosphatidylethanolamine IgM and anti-dsDNA IgG. Seroprevalence of elevated serum autoantibodies constituted 70.8% before and 75% after vaccination. According to the results, immunization with Gam-COVID-Vac does not affect ovarian reserve or autoimmune status, thus being safe for the female reproductive potential.

Pregnancy outcomes after maternal covid-19 vaccination during pregnancy: Preliminary data

COVID-19 significantly raises risk during pregnancy. Currently, available evidence suggests that pregnant women are more susceptible to COVID-19 than the general population [1]. Pregnant women with COVID-19 are at increased risk of severe illness, death, and adverse pregnancy outcomes [2–4]. The most effective way to prevent the disease is vaccination. Current research evidence suggests that approved COVID-19 vaccines are safe, effective, and unlikely to pose any dangers to pregnant women or fetuses [5]. National and international associations issued guidelines supporting COVID-19 vaccination in pregnant and lactating women [6]. In the Russian Federation, vaccination of pregnant women with the Gam-COVID-Vac (Sputnik V) vaccine has been permitted since June 2021. Results of animal preclinical studies suggest no adverse impact of the Gam-COVID-Vac vaccine on the course of pregnancy and fetal, embryonic, and prenatal development of offspring [7]. Objective: This study aimed to analyze pregnancy complications after maternal COVID-19 vaccination with domestic vaccines during pregnancy. Region, 75 from Trans-Baikal Krai, 76 from Yaroslavl Region, 89 from Yamalo-Nenets Autonomous Okrug, and 92 from Sevastopol. Most of the women were vaccinated with Gam-COVID-Vac (Sputnik V) vaccine (91.6%) and received two vaccine doses (57.9%). Most of the patients were vaccinated in the first trimester of pregnancy, including 683 (88.4%), 51 (6.6%), and 39 (5%) before 12 weeks, from 12 to 22 weeks, and after 22 weeks of pregnancy, respectively.

Morphometric Parameters of Placental Villi in Parturient Women with COVID-19.

We performed a comparative morphological analysis of placental villi in parturient women with mild and moderate COVID-19 infection. The area and perimeter of terminal villi, their capillaries, and syncytiotrophoblast were assessed on immunohistochemical preparations with antibodies to CD31 using an image analysis system; the parameters of fetal vascular component in the placental villi were also assessed. Changes in the studied parameters differed in parturient women with mild and moderate COVID-19 infection. The observed increase in the total perimeter with a simultaneous decrease in the total capillary area and the degree of vascularization of the placental villi in parturient women with COVID-19 indicates impairment of circulation in the fetal compartment and the development of placental hypoxia, which can be the cause of unfavorable neonatal outcomes.

Immune status of covid-19 patients with different disease severity

Aim. To investigate the immune status and compare immunological parameters in COVID-19 patients with different disease severity. Materials and methods. The prospective study included 62 patients with COVID-19. The patients were stratified into three groups based on the disease severity, including mild (group 1, n=29), moderate (group 2, n=17), and severe (group 3, n=16) forms of COVID-19. On days 3–7 from the onset of the disease, peripheral blood lymphocytes were phenotyped by flow cytometry. Cytokine concentrations were measured using a multiplex immunoassay-standard 48-plex Bio-Plex Pro™ Human Cytokine Screening test system (Bio-Rad, USA) on a flow-based laser immuno-analyzer Bio-Plex 200. Results. Patients with severe COVID-19 had higher levels of leukocytes, neutrophils, CRP, and lower relative and absolute lymphocyte counts. There were low counts of CD3+, CD3+CD4+, CD3+CD8+, and T-lymphocytes expressing the activation marker HLA-DR (CD3+HLA-DR+), NK-cells, and PAN. In group 3, changes in 39 of the 48 investigated soluble factors were observed. Conclusion. High levels of leukocytes, neutrophils, CRP, neutrophilic-leukocyte index, low levels of absolute and relative lymphocyte counts, pronounced changes in immunological parameters, a systemic inflammatory reaction associated with the release of mediators called cytokines ("cytokine storm") predispose to a severe course of COVID-19. © A group of authors, 2021.

Gam-covid-vac (Sputnik v) vaccine has no adverse effect on ovarian reserve in reproductive-age women

Relevance. There is limited evidence on the effect of various vaccines on the human reproductive system. Potential adverse effects of vaccines on fertility are associated with autoimmune disorders, which might cause gonadal damage. Currently, several studies are underway investigating the impact of COVID-19 vaccines on human fertility. To our best knowledge, there is only one study published which demonstrated no adverse effects of the COVID-19 vaccine on assisted reproductive technology outcomes. Aim. To investigate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on ovarian reserve and antiphospholipid antibody level in reproductive-age women. Materials and methods. The prospective study included 51 women vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V) vaccine. The inclusion criteria were age from 18 to 45, preserved menstrual function, normal ovarian reserve, no history of COVID-19, negative PCR test result for SARS-CoV-2 and negative SARS-CoV-2 IgG antibody test before vaccination, no pregnancy, and no history of serious illnesses. Clinical evaluation was carried out twice-immediately before immunization and 90 days after the first vaccine component administration. The antral follicle count was measured by pelvic ultrasound. Serum levels of AMH, FSH, TSH, estradiol, antiphospholipid antibodies (aPL) M and G isotypes against cardiolipin (aCL), β2-glycoprotein-1 (aβ2-GP-1), annexin V (aAn V), phosphatidylserine (aPS), and IgG antibodies against SARS-CoV-2 were measured by enzyme immunoassay. Results. There were no significant changes in hormones levels and antral follicle counts before and after vaccination, including in women of advanced reproductive age (≥37 years). After immunization, aPL antibody levels did not differ significantly from the baseline. There was no correlation between aPL antibody level dynamics and level of FSH and AMH, which indirectly demonstrates no possible autoimmune effect of vaccination on women's fertility. Conclusion. This is the first study investigating the effect of the Gam-COVID-Vac vaccine on ovarian reserve parameters and aPL antibody levels. The preliminary results prove that the Gam-COVID-Vac vaccine in women of reproductive age does not adversely impact ovarian reserve.

Gam-covid-vac (Sputnik v) vaccine has no adverse effect on spermatogenesis in men

Relevance. During the pandemic and large-scale vaccination against COVID-19, studies of the effect of various types of vaccines on human reproductive function have become particularly important. Vaccination may have a negative impact on the reproductive organs and tissues due to the development of an autoimmune process involving the gonads. Currently, there are some studies on the effect of vaccination against coronavirus infection caused by SARS-CoV2 on the male and female reproductive function. The absence of a negative effect of vaccination on spermatogenesis in men has already been demonstrated in the results of three studies. Objective. To evaluate the effect of the Gam-COVID-Vac (Sputnik V) vaccine on spermatogenesis and the level of antiphospholipid antibodies in men. Materials and methods. The prospective study included 45 men who were vaccinated against COVID-19 with Gam-COVID-Vac (Sputnik V). The criteria for inclusion in the study were the age from 18 to 55 years, the absence of a previous history of COVID-19, a negative RT-PCR result in SARS-CoV-2 testing, negative SARS-CoV-2 IgG results prior to vaccination, and the absence of severe somatic diseases. The patients were examined twice: immediately before vaccination and 90 days after the first dose was injected. We evaluated spermogram parameters, determined the levels of FSH, LH, TSH and total testosterone, and analyzed blood for IgM and IgG antiphospholipid antibodies (aPL) to cardiolipin (aCL), β2-glycoprotein-1 (aß2-GP1), annexin V (aAnV), phosphatidylserine (aPS), as well as IgG antibodies to SARS-CoV-2 using enzyme immunoassay. Results. There were no significant changes in the parameters of spermogram and hormone levels before and after vaccination;men with moderate impairment of spermatogenesis (oligoasteno-and/or teratozoospermia) did not show considerable changes either. The level of aPL after vaccination did not increase compared to the baseline level. Besides, there was no correlation between the dynamics of the level of antisperm antibodies, aPL and spermogram parameters. These findings indirectly indicate that there are no changes in the reproductive function associated with this autoimmune factor after vaccination in men. Conclusion. This is one of the first studies that has revealed the effect of the Gam-COVID-Vac vaccine on spermatogenesis, hormonal profile and aPL level in men. The obtained results demonstrate that the Gam-COVID-Vac vaccine does not have a negative effect on the reproductive function in men.

The Number of Syncytial Knots and VEGF Expression in Placental Villi in Parturient Woman with COVID-19 Depends on the Disease Severity.

A comparative morphological study was carried out to analyze the number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 categorized by the disease severity. The number of syncytial knots was assessed on specimens stained with hematoxylin and eosin. VEGF expression was determined by immunohistochemical analysis in syncytiotrophoblast and villous endothelial cells. Morphological study of the placenta tissue of parturient women with COVID-19 showed increased numbers of syncytial knots in the villi, indicating the development of preplacental hypoxia. High VEGF expression in syncytiotrophoblast and vascular endotheliocytes reflects a stereotyped response to hypoxia and can underlie the development of a preeclampsia-like syndrome. The number of syncytial knots and VEGF expression in placental villi in parturient women with COVID-19 depended on the disease severity.

The effect of vaccines on the reproductive system

The authors carried out a systematic analysis of the data available in the modern literature on the effect of different types of vaccines on the male and female reproductive system. The review includes data from publications presented in the PubMed database (https://pubmed.ncbi.nlm.nih.gov/) on this topic. It gives information on the types of vaccines. The paper describes possible adverse events (AEs) due to vaccine administration, as well as the development of autoimmune diseases and AEs associated with the effect of antibody-dependent enhancement. Particular attention is paid to the analysis of the available data on the effect of different types of vaccines, including coronavirus vaccines, on the reproductive system of mammals, including humans, and the genesis of their occurrence, in particular the autoimmune-mediated mechanism of damage to the reproductive organs. Conclusion. Taking into account that the literature does not describe a single prospective study that would investigate the effect of vaccines on human reproductive function, or data on the possible negative effect of vaccines are conjectural or based on the follow-up findings in patients without prior examination of their reproductive status, it is necessary to conduct further investigations of the effect of different types of vaccines on reproductive function.

The impact of the immune status on COVID-19 severity

Aim. To investigate the impact of patient immune status on the severity of COVID-19. Materials and methods. The prospective study included 63 employees of the V.I. Kulakov NMRC for OG&P of Minzdrav of Russia with confirmed COVID-19. The patients were stratified into three groups based on the disease severity, including asymptomatic (group 1, n=17), mild (group 2, n=29), and moderate (group 3, n=17) form of COVID-19. On days 3–7 from the onset of the disease, peripheral venous blood samples were collected from the study subjects and tested for serum levels of anti-SARS-CoV-2 IgG antibodies and immune profile by ELISA. After day 20+, testing for serum levels of anti-SARS-CoV-2 IgG antibodies was repeated using ELISA. Results. Patients who had a higher BMI, blood group A(II), lower leukocyte and lymphocyte counts, higher relative monocyte count, changes in the immune profile in the form of a lower number of CD3+, CD3+ CD8+, СD19+, CD19+ CD5+, and phagocytic activity of neutrophils, developed more severe forms of COVID-19. They had severe clinical manifestations of the disease, and 100% of them developed antiviral immunity. Conclusion. This study identified several clinical, laboratory, and immune profile features that may be considered as predictive factors of severe COVID-19 and can be used in clinical practice to predict the clinical course of the disease.