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Abstract
Post-COVID-19 may be accompanied by the prolonged persistence of immune and vascular disorders. At the same time, the characteristics of interferon alpha expression in the placenta during pregnancy that occurs 6-12 months after the disease have not been sufficiently studied.
The purpose of the study is a comparative assessment of IFNα expression in placentas from full-term gestation in patients who had COVID-19 6-12 months – before conception, with a comparison of their clinical and anamnestic data and the histological features of the placentas.
Materials and methods. A retrospective cohort study of 40 full-term placentas was performed. The main group comprised 20 patients who had COVID-19 before conception; the comparison group comprised 20 patients without COVID-19 history. Somatic pathology, pregnancy complications and placental histology were analyzed. Immunohistochemistry for IFN-α was performed using polyclonal antibodies; expression was assessed as the percentage of immunopositive syncytiotrophoblast area using digital image analysis (QuPath software). Statistical analysis was performed using SPSS Statistics 26.0.
Results. The groups were comparable in age and gestational age at delivery. IFN-α expression in placentas of group 1 was significantly lower compared to group 2 (68.99 ± 3.84% vs. 78.67 ± 3.76%; p < 0.001). In the medical history, patients in group 1 had a significantly higher frequency of uterine scar (5/20 – 25% vs. 0/20 – 0%, p = 0.017) and previous preterm births (4/20 – 20% vs. 0/20 – 0%, p = 0.035). Among pregnancy complications, anemia was less common in group 1 (5/20 – 25% vs. 13/20 – 65%, p = 0.011). Placentas in group 1 showed significantly more frequent signs of maternal and fetal vascular malperfusion.
Conclusion. In patients who had COVID-19 6-12 months before pregnancy, full-term placentas show persistently reduced IFN-α expression, associated with morphological signs of vascular malperfusion, reflecting ongoing immune and vascular dysregulation. This justifies classifying such women as a high-risk group for placental disorders and the need for preconception care.
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References
1. Kostinov MP. Immunopathogenic properties of SARS-CoV-2 as a basis for the choice of pathogenetic therapy. Immunologiya. 2020; 41(1): 83-91. Russian (Костинов М.П. Иммунопатогенные свойства SARS-CoV-2 как основа для выбора патогенетической терапии //Иммунология. 2020. Т. 41, № 1. С. 83-91.) doi: 10.33029/0206-4952-2020-41-1-83-91
2. Adamyan LV, Vechorko VI, Konysheva OV, Kharchenko EI, Doroshenko DA. Post-COVID-19 syndrome in obstetrics and reproductive medicine. Russian Journal of Human Reproduction. 2021; 27(6): 30-40. Russian (Адамян Л.В., Вечорко В.И., Конышева О.В., Харченко Э.И., Дорошенко Д.А. Постковидный синдром в акушерстве и репродуктивной медицине //Проблемы репродукции. 2021. Т. 27, № 6. С. 30-40.) doi: 10.17116/repro20212706130
3. Belokrinitskaya TE, Frolova NI, Mudrov VA, Kargina KA, Shametova EA, Zhamyanova ChTs, Osmonova ShR. Post-COVID-19 syndrome in early reproductive age women. Obstetrics and Gynecology. 2023; (7): 47-54. Russian (Белокриницкая Т.Е., Фролова Н.И., Мудров В.А., Каргина К.А., Шаметова Е.А., Жамьянова Ч.Ц., Осмонова Ш.Р. Постковидный синдром у женщин раннего репродуктивного возраста //Акушерство и гинекология. 2023. № 7. С. 47-54.) doi: 10.18565/aig.2023.67
4. Osikov MV, Antonov VN, Zotov SO. Three-year prognosis of complications in patients after COVID-19. Avicenna Bulletin. 2025; 27(2): 291-305. Russian (Осиков М.В., Антонов В.Н., Зотов С.О. Трехлетний прогноз возникновения осложнений у больных после перенесенного COVID-19 //Вестник Авиценны. 2025. Т. 27, № 2. С. 291-305.) doi: 10.25005/2074-0581-2025-27-291-305
5. Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234): 1417-1418. doi: 10.1016/S0140-6736(20)30937-5
6. Chen C, Haupert SR, Zimmermann L, Shi X, Fritsche LG, Mukherjee B. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. J Infect Dis. 2022; 226(9): 1593-1607. doi: 10.1093/infdis/jiac136
7. Flores-Vega VR, Monroy-Molina JV, Jiménez-Hernández LE, Torres AG, Santos-Preciado JI, Rosales-Reyes R. SARS-CoV-2: evolution and emergence of new viral variants. Viruses. 2022; 14(4): 653. doi: 10.3390/v14040653
8. Fink NR, Chawes B, Bønnelykke K, Thorsen J, Stokholm J, Rasmussen MA, et al. Levels of systemic low-grade inflammation in pregnant mothers and their offspring are correlated. Sci Rep. 2019; 9: 3043. doi: 10.1038/s41598-019-39620-5
9. Casazza RL, Lazear HM, Miner JJ. Protective and pathogenic effects of interferon signaling during pregnancy. Viral Immunol. 2020; 33(1): 3-11. doi: 10.1089/vim.2019.0076
10. Park A, Iwasaki A. Type I and type III interferons: induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020; 27(6): 870-878. doi: 10.1016/j.chom.2020.05.008
11. Ding J, Maxwell A, Adzibolosu N, Hu A, You Y, Liao A, Mor G. Mechanisms of immune regulation by the placenta: role of type I interferon and interferon-stimulated genes signaling during pregnancy. Immunol Rev. 2022; 308(1): 9-24. doi: 10.1111/imr.13077
12. Milovanov AP, Fokina TV. The decisive importance of constitutional interferons in human and animal ontogenesis. Arkhiv Patologii. 2018; 80(6): 68-72. Russian (Милованов А.П., Фокина Т.В. Определяющее значение конституциональных интерферонов в онтогенезе человека и животных //Архив патологии. 2018. Т. 80, № 6. С. 68-72.) doi: 10.17116/patol20188006168
13. Milovanov AP, Voloshchuk IN. Deported syncytiotrophoblast and placental microparticles in the mother’s body during normal pregnancy and preeclampsia (28 years later). Arkhiv Patologii. 2017; 79(1): 61-67. Russian (Милованов А.П., Волощук И.Н. Депортированный синцитиотрофобласт и плацентарные микрочастицы в организме матери при нормальной беременности и преэклампсии (28 лет спустя) //Архив патологии. 2017. Т. 79, № 1. С. 61-67.) doi: 10.17116/patol201779161-67
14. Matsuyama T, Kubli SP, Yoshinaga SK, Pfeffer K, Mak TW. An aberrant STAT pathway is central to COVID-19. Cell Death Differ. 2020; 27(12): 3209-3225. doi: 10.1038/s41418-020-00633-7
15. Coler B, Wu TY, Carlson L, Burd N, Munson J, Dacanay M, et al. Diminished antiviral innate immune gene expression in the placenta following a maternal SARS-CoV-2 infection. Am J Obstet Gynecol. 2023; 228(4): 463.e1-463.e20. doi: 10.1016/j.ajog.2022.09.023
16. Pell R, Oien K, Robinson M, Pitman H, Rajpoot N, Rittscher J, et al. The use of digital pathology and image analysis in clinical trials. J Pathol Clin Res. 2019; 5(2): 81-90. doi: 10.1002/cjp2.127