Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
+44 1223 790975
ISSN: 2155-9899
+44 1223 790975
Short Communication - (2023)Volume 14, Issue 5
The observational prospective study included 240 women aged 18-40 years without systemic autoimmune diseases who applied for infertility treatment using ART. Patients were divided into two groups: group 1-105 patients without a history of COVID-19; group 2-135 patients who survived mild (n=85) or moderate COVID-19 (n=50) less than 12 months prior to Transvaginal Oocyte Retrieval (TOR). The new RNA Betacoronavirus SARS-CoV-2 in 2019 was the cause the first cases of COVID-19 in humans, and in March 2020 WHO announced a COVID-19 pandemic. SARSCoV- 2 infection can trigger such immunopathological mechanisms as inflammation, apoptosis, endothelial dysfunction, cytokine storm, complement and coagulation hyperactivation.
Autoantibody profile; Autoimmune disease; Transvaginal oocyte retrieval; Apoptosis
The new RNA Betacoronavirus SARS-CoV-2 in 2019 was the cause the first cases of COVID-19 in humans, and in March 2020 World Health Organization (WHO) announced a COVID-19 pandemic. SARS-CoV-2 infection can trigger such immunopathological mechanisms as inflammation, apoptosis, endothelial dysfunction, cytokine storm, complement and coagulation hyperactivation [1]. Remarkably, the expression of Angiotensin-Converting Enzyme 2 (ACE2), the main cellular Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV- 2) receptor, and co-receptor transmembrane serine protease 2 was found not only in epithelial cells of respiratory tract, but also in cells of the endometrium, placenta, ovaries, fallopian tubes, and embryo [2]. Moreover, ACE2 is an important component of the renin-angiotensin system, dysregulation of the latter can lead to impaired folliculogenesis, ovulation, and corpus luteum function [3].
In addition, SARS-CoV-2 share similarities with other viruses that trigger autoimmunity: induce production of autoantibodies, cause a strong type I interferon response, trigger autoimmune disorders in susceptible people [4]. Moreover, viral proteins, in particular the S protein, contain superantigenic motifs and peptide sequences homologous to fragments of human proteins. In severe COVID-19, the development of B-lymphocytes and plasma cells from naive B-cells can be carried out along the extrafollicular pathway [5]. All of the above predisposes to triggering an autoimmune process that can affect fertility or Assisted Reproductive Technology (ART) outcomes.
We investigated the effect of COVID-19 of varying severity and associated autoantibodies on reproductive outcomes in ART cycles with fresh oocytes retrieved at different time intervals after the disease [6].
The observational prospective study included 240 women aged 18-40 years without systemic autoimmune diseases who applied for infertility treatment using ART from September 2020 to December 2021. Patients were divided into two groups: group 1-105 patients without a history of COVID-19; group 2-135 patients who survived mild (n=85) or moderate COVID-19 (n=50) less than 12 months prior to Transvaginal Oocyte Retrieval (TOR).
To confirm the diagnosis of COVID-19 and detect re-infection, nasopharyngeal swabs were screened using real-time reverse transcription polymerase chain reaction, and serum antibodies to SARS-CoV-2 were determined using Enzyme-Linked Immunoassay (ELISA). The profile of serum autoantibodies, including Antiphospholipid (aPL), antinuclear and anti-thyroid antibodies, was studied prior to the ART cycle.
In all ART cycles, a protocol of controlled ovarian stimulation with a gonadotropin-releasing hormone antagonist was used [6]. The frequency of intracytoplasmic sperm injection for egg fertilization in two groups did not differ (86.7% vs. 91.8%; p=0.192), in other cases, in vitro fertilization was used.
Group 2 differed from group 1 by a higher body mass index in patients and a higher incidence of ear, throat, nose diseases and allergic disorders, 93.3% of them had Immunoglobulin G (IgG) antibodies against SARS-CoV-2. No differences were found between the parameters of oogenesis, embryogenesis, pregnancy and live birth rates in patients of these groups, as well as in patients with mild or moderate COVID-19. However, when TOR was performed less than 180 days after COVID-19, a higher proportion of poor quality blastocysts was obtained (p=0.006). Moreover, the risk of early miscarriage in patients with moderate COVID-19 was 4.2 times higher than in patients without a history of COVID-19 (p=0.036).
Although the rate of detection of total aPL in two groups did not differ (29.5%; 31.3%; p=0.79), in group 2, antibodies to Phosphatidylethanolamine (PE) and Annexin V (An V) were revealed more often than “criteria” aPL (to cardiolipin, β2-glycoprotein-I). IgG antibodies to PE and An V were detected in-group 2 (8.1%; 6.7%) and in subgroup 2b (8%; 10%) more often compared with group 1 (0.95%; 1.9%; p<0.05). The median level of anti-PE IgG was higher in group 2 than in group 1. Moreover, IgG antibodies to the Thyroid Stimulating Hormone Receptor (TSHr) were revealed more often in post-COVID-19 patients (8.2% vs. 1.9%, p=0.033). A negative correlation was found between the level of anti-PE IgG and the number of obtained mature oocytes (r=-0.129, p=0.045) and zygotes (r=-0.132, p=0.041). Remarkably, antibodies to PE and An V were found in 3 out of 6 patients with early miscarriage.
In non-vaccinated patients who have had mild and moderate COVID-19 less than 12 months before TOR, parameters of oogenesis and embryogenesis, rate of pregnancy in ART cycles did not differ from those in patients without a history of COVID-19. However, patients who had survived COVID-19 less than 180 days prior to TOR had a higher proportion of poor quality blastocysts, and patients with moderate COVID-19 had an increased rate of early miscarriage. In post-COVID-19 patients, there was a higher frequency of detection of antibodies to PE and An V, as well as antibodies to TSHr, and an inverse correlation between the level of anti-PE IgG and the number of obtained oocytes and zygotes. All of the above suggests a possible adverse effect of COVID-19 and associated autoantibodies on the outcomes of ART cycles and early pregnancy. Clinical and laboratory monitoring, including autoantibody screening, in post-COVID-19 patients will allow to identify autoimmune disorders that may affect reproductive outcomes.
This research has been supported by the "Investment in the Future" Charitable Foundation as part of the "Let's Stop the Coronavirus Together" campaign.
The authors declare no conflict of interest.
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Citation: Dolgushina NV, Menzhinskaya IV, Ermakova DM, Frankevich NA, Vtorushina VV, Sukhikh GT (2023) Potential Relationship between Recent COVID-19, Autoantibody Profile, and Outcomes of Assisted Reproductive Technology Cycles in Non-Vaccinated Women. J Clin Cell Immunol. 14:696.
Received: 22-Aug-2023, Manuscript No. JCCI-23-26270; Editor assigned: 24-Aug-2023, Pre QC No. JCCI-23-26270 (PQ); Reviewed: 08-Sep-2023, QC No. JCCI-23-26270; Revised: 15-Sep-2023, Manuscript No. JCCI-23-26270 (R); Published: 22-Sep-2023 , DOI: 10.35248/2155-9899.23.14.696
Copyright: © 2023 Dolgushina NV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.