ABSTRACT
Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, beta 2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%);p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy.
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS) that affects fertility in women. Antibodies against ACE2 have predictive value for COVID-19 and may contribute to RAS dysregulation and reproductive failure. Objective(s): To investigate the prevalence and levels of anti-ACE2 autoantibodies in infertile patients with a history of COVID-19 and in fertile women. Material(s) and Method(s): Serum anti-ACE2 autoantibodies (M, G) were determined by ELISA in infertile patients with a history of COVID-19 (group 1, n=121), without a history of COVID-19 (group 2, n=79), and in fertile women (group 3, n=80). The association between antibodies against ACE2, SARS-CoV-2, thyroid antigens, and hormones was investigated. Result(s): Patients in groups 1 and 2 had higher rates of inflammatory gynecologic diseases, pelvic surgery, spontaneous miscarriages, and thyroid pathology than those in group 3. Anti-ACE2 antibodies were detected more frequently (40.5% and 38.8 %) and had higher levels in infertile patients than in fertile women (20%). Women with a history of COVID-19 were more likely to have anti-ACE2 IgG. Antibodies against ACE2 were significantly correlated with those against FSH. Conclusion(s): Patients with infertility, irrespective of a history of COVID-19, have a higher prevalence and higher anti-ACE2 antibody levels than fertile women. Anti-ACE2 antibodies are associated with primary and secondary infertility, and may be involved in the pathophysiology of infertility.Copyright © A group of authors, 2023.
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS) that affects fertility in women. Antibodies against ACE2 have predictive value for COVID-19 and may contribute to RAS dysregulation and reproductive failure. Objective(s): To investigate the prevalence and levels of anti-ACE2 autoantibodies in infertile patients with a history of COVID-19 and in fertile women. Material(s) and Method(s): Serum anti-ACE2 autoantibodies (M, G) were determined by ELISA in infertile patients with a history of COVID-19 (group 1, n=121), without a history of COVID-19 (group 2, n=79), and in fertile women (group 3, n=80). The association between antibodies against ACE2, SARS-CoV-2, thyroid antigens, and hormones was investigated. Result(s): Patients in groups 1 and 2 had higher rates of inflammatory gynecologic diseases, pelvic surgery, spontaneous miscarriages, and thyroid pathology than those in group 3. Anti-ACE2 antibodies were detected more frequently (40.5% and 38.8 %) and had higher levels in infertile patients than in fertile women (20%). Women with a history of COVID-19 were more likely to have anti-ACE2 IgG. Antibodies against ACE2 were significantly correlated with those against FSH. Conclusion(s): Patients with infertility, irrespective of a history of COVID-19, have a higher prevalence and higher anti-ACE2 antibody levels than fertile women. Anti-ACE2 antibodies are associated with primary and secondary infertility, and may be involved in the pathophysiology of infertility.Copyright © A group of authors, 2023.
ABSTRACT
Angiotensin-converting enzyme 2 (ACE2) is a key component of the renin-angiotensin system (RAS) that affects fertility in women. Antibodies against ACE2 have predictive value for COVID-19 and may contribute to RAS dysregulation and reproductive failure. Objective(s): To investigate the prevalence and levels of anti-ACE2 autoantibodies in infertile patients with a history of COVID-19 and in fertile women. Material(s) and Method(s): Serum anti-ACE2 autoantibodies (M, G) were determined by ELISA in infertile patients with a history of COVID-19 (group 1, n=121), without a history of COVID-19 (group 2, n=79), and in fertile women (group 3, n=80). The association between antibodies against ACE2, SARS-CoV-2, thyroid antigens, and hormones was investigated. Result(s): Patients in groups 1 and 2 had higher rates of inflammatory gynecologic diseases, pelvic surgery, spontaneous miscarriages, and thyroid pathology than those in group 3. Anti-ACE2 antibodies were detected more frequently (40.5% and 38.8 %) and had higher levels in infertile patients than in fertile women (20%). Women with a history of COVID-19 were more likely to have anti-ACE2 IgG. Antibodies against ACE2 were significantly correlated with those against FSH. Conclusion(s): Patients with infertility, irrespective of a history of COVID-19, have a higher prevalence and higher anti-ACE2 antibody levels than fertile women. Anti-ACE2 antibodies are associated with primary and secondary infertility, and may be involved in the pathophysiology of infertility.Copyright © A group of authors, 2023.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Investigation of the effect COVID-19 mediated with autoantibodies has on reproductive outcomes is important. This study aimed to evaluate the profile of antiphospholipid antibodies (aPL) and their association with the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19. The study included 240 patients: 105 of them did not have a history of COVID-19 (group 1) and 135 of them had a history of COVID-19 (group 2) with a mild course (subgroup 2a, n = 85) or moderate course (subgroup 2b, n = 50). With the help of ELISA, serum antibodies (M, G) to cardiolipin, beta2-glycoprotein-I, annexin V (AnV), phosphatidylethanolamine (PE), phosphatidylserine, and phosphatidylserine/prothrombin complex were determined. The evaluated parameters were the indices of oogenesis, embryogenesis, ART intervention outcomes. In group 2, growing levels of anti-AnV and anti-PE IgG were observed more often (in 28 (20.7%) and 8 (5.9%) patients) than in group 1 (in 10 (9.5%) and 1 (0.95%);p = 0.02 and p = 0.045, respectively). In subgroup 2b we registered a higher level of anti-PE IgG and a higher incidence of early miscarriages (in 6 (12%) patients) than in group 1 (in 3 (2.9%)) (p = 0.024). Weak inverse correlations were found between the level of anti-PE IgG and the number of oocytes and zygotes. The results of this study suggest a negative impact of aPL-mediated COVID-19 on the outcomes of ART programs and the course of early pregnancy. Copyright © 2022 Pirogov Russian National Research Medical University. All rights reserved.
ABSTRACT
Objective: To investigate the outcomes of assisted reproductive technology (ART) programs in patients with a history of COVID-19 of various severity. Material(s) and Method(s): This prospective study enrolled 240 infertile patients. They were divided into group 1 comprising patients without a history of COVID-19 (n=105) and group 2 (n=135) including patients who less than 12 months before the ART cycle had mild (subgroup 2a, n=85) or moderate (subgroup 2b, n=50) COVID-19. The level of specific antibodies to SARS-CoV-2, parameters of oogenesis, early embryogenesis, and clinical outcomes of HRT were evaluated. Result(s): The parameters of oogenesis and embryogenesis, pregnancy and delivery rates did not differ between groups 1 and 2. A weak negative correlation was detected between the level of IgG-antibodies to SARS-CoV-2 and the number of obtained oocytes and embryos. Patients with an interval between COVID-19 and ART cycle <=6 months had a significantly higher relative number of poor-quality blastocysts than women with >6 months interval. Patients who experienced moderate COVID-19 had a high early miscarriage rate of (12%). Conclusion(s): COVID-19 can adversely affect reproductive outcomes, lead to a decrease in the number of oocytes and embryos obtained in ART cycles and their quality, and increase the risk of early miscarriage. More research is needed to investigate the mechanisms underlying the adverse effects of COVID-19 and the post-COVID syndrome. Copyright © A group of authors, 2022.
ABSTRACT
COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, may predispose to thrombotic events, especially when combined with antiphospholipid antibodies (aPL). However, there are limited data on prevalence and antigenic specificity of aPL in COVID-19. Complement activation is assumed to play an important role in pathogenesis of COVID-19-associated coagulopathy. During the SARS-CoV-2 pandemic, it is necessary to identify important biomarkers for predicting severe course of COVID-19 and risk of thrombotic complications. Our objective was to evaluate the aPL profile, quantitative content and activity of complement and its components in COVID-19 patients graded by severity in the course of time. IgM and IgG antibodies to cardiolipin (CL), phosphatidylserine (PS), β2-glycoprotein-I (β2-GP-I), prothrombin (PT), annexin V (An V), as well as C1q complement component, content of its C3 and C4 components and total complement activity were determined in blood serum using ELISA approach. 141 patients with COVID-19 were included in the study. Group 1 consisted of 39 patients with mild form, group 2 (65 patients) presented with moderate form, and group 3 included 37 patients with severe form of COVID-19. Blood samples were obtained on day 3-7 of the disease (1st point) and after 14-28 days (2nd point). The results were as follows: aPL were detected in 29.1% of the total COVID-19 cohort, frequency of aPL detection by the severity grade did not differ (33.3%, 24.6% and 32.4%). In 8.5% of the patients, aPL were detected only at the 1st time point;in 14.2%, only at the 2nd point;and in 6.4% of the cases, at the both time points. Antibodies to PT (16.3%) and An V (11.3%) were revealed more frequently. The detection frequency of antibodies to PT was significantly higher than antibodies to CL and PS (7.1%), β2-GP-I (7.8%). The prevalence of aPL in groups 1 and 3 did not differ. At the 1st point in group 3, increased levels of C4 (89.2%) and C3 (24.3%) in blood, and a decrease in complement activity (35.1%) were more often observed than in group 1. At the 2nd time point in group 3, a decrease in complement activity was often detected (59.5%). The C3 levels exceeding 720 μg/ml were found to predict a 2.6-fold increased risk of severe COVID-19, and this risk became 3.3 times higher at C4 levels of > 740 μg/ml. The antibodies to PT and An V are often detected in COVID-19 patients, along with low prevalence of antibodies to CL and β2-GP-I. These antibodies can be involved in pathogenesis of COVID-19-associated coagulopathy, being detectable at the late stage of the disease, and they may trigger APS in predisposed patients and reconvalescents. Although presence of aPL antibodies is not associated with COVID-19 severity, their persistence over the period of convalescence may be an additional risk factor for thromboembolic complications. The COVID-19 patients are characterized by activation of the complement system, which increases in severe cases, and manifests with increased or decreased levels of C3 complement component, increased levels of C4 component in blood, and a decreased total complement activity. Quantitative determination of C3 and C4 complement components over the period of COVID-19 progression is of prognostic value, with respect to severity of the disease.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.