Pathomorphological ultrastructural changes in the placenta in coronavirus disease 2019 (COVID-19) during pregnancy: a literature review

Authors

DOI:

https://doi.org/10.14739/mmt.2026.2.344103

Keywords:

COVID-19, SARS-CoV-2, pregnancy, placenta, chorionic villi, telocytes

Abstract

Aim. Based on the analysis of literature data, to investigate the pathomorphological and ultrastructural changes in the placenta associated with COVID-19 during pregnancy, with the identification of critical periods for fetal development.

Materials and methods. A search for original research articles was conducted in the scientometric databases PubMed, Web of Science, Scopus, and Google Scholar published between 2017 and 2025. The following search terms were used: COVID-19, SARS-CoV-2, placenta, pregnancy, chorionic villi, and placental telocytes. A total of 44 publications were selected to summarize current knowledge on the issue.

Results. According to the literature, during the acute phase of COVID-19 in pregnant women, 100 % of cases showed placentitis, signs of endothelial dysfunction, damage to the microcirculatory bed, edema of the chorionic villi stroma, nuclear apoptosis, narrowing of the vascular lumen, and destructive changes in telocytes. As the post-COVID interval lengthened, manifestations of placentitis decreased and vascular lumens were restored (in cases of COVID-19 during the third trimester). In contrast, cases of infection in the second trimester were characterized by arteriolosclerosis, stromal fibrosis of the villi, and delayed chorionic maturation.

Conclusions. Vertical transmission of SARS-CoV-2 from infected pregnant women to their fetuses has been demonstrated, with no established correlation between the severity of maternal illness and the extent of placental or fetal impairment. The SARS-CoV-2 virus causes endothelial dysfunction, microcirculatory disturbances, edema, and placentitis, acting as a morphogenetic factor in chorionic remodeling. The degree of placental pathomorphological changes and the consequences for the fetus were determined by the gestational age at which maternal infection occurs. The loss of regulatory control by structurally damaged telocytes over angiogenesis, vascular tone regulation, and apoptosis constitutes one of the mechanisms underlying the development of placental insufficiency.

Author Biographies

T. V. Savchuk, Bogomolets National Medical University, Kyiv

MD, PhD, Associate Professor of the Department of Pathological Anatomy

I. V. Leshchenko, Bogomolets National Medical University, Kyiv

PhD, Senior Lecturer of the Department of Physiology

References

  1. Turco MY, Gardner L, Kay RG, Hamilton RS, Prater M, Hollinshead MS, et al. Trophoblast organoids as a model for maternal–fetal interactions during human placentation. Nature. 2018;564(7735):263-7. doi: https://doi.org/10.1038/s41586-018-0753-3
    | |
  2. Kidron D, Vainer I, Fisher Y, Sharony R. Automated image analysis of placental villi and syncytial knots in histological sections. Placenta. 2017;53:113-8. doi: https://doi.org/10.1016/j.placenta.2017.04.004
    | |
  3. Leavey K, Benton SJ, Grynspan D, Bainbridge SA, Morgen EK, Cox BJ. Gene markers of normal villous maturation and their expression in placentas with maturational pathology. Placenta. 2017;58:52-9. doi: https://doi.org/10.1016/j.placenta.2017.08.005
    | |
  4. Farah O, Nguyen C, Tekkatte C, Parast MM. Trophoblast lineage-specific differentiation and associated alterations in preeclampsia and fetal growth restriction. Placenta. 2020;102:4-9. doi: https://doi.org/10.1016/j.placenta.2020.02.007
    | |
  5. Rao Sudhakara M, Sailaja G, Deepika K. The relationship between the weight of the placenta and birth weight of neonate in Konaseema area, east Godavari, Andhra Pradesh. MedPulse International Journal of Anatomy. 2021;19(1):6-9. doi: https://doi.org/10.26611/10011912
  6. Arutyunyan A, Roberts K, Troulé K, Wong FCK, Sheridan MA, Kats I, et al. Spatial multiomics map of trophoblast development in early pregnancy. Nature. 2023;616(7955):143-51. doi: https://doi.org/10.1038/s41586-023-05869-0
    | |
  7. Anto EO, Coall DA, Asiamah EA, Afriyie OO, Addai-Mensah O, Wiafe YA, et al. Placental lesions and differential expression of pro-and anti-angiogenic growth mediators and oxidative DNA damage marker in placentae of Ghanaian suboptimal and optimal health status pregnant women who later developed preeclampsia. PLoS One. 2022;17(3):e0265717. doi: https://doi.org/10.1371/journal.pone.0265717
    | |
  8. Edlow AG, Li JZ, Collier AY, Atyeo C, James KE, Boatin AA, et al. Assessment of Maternal and Neonatal SARS-CoV-2 Viral Load, Transplacental Antibody Transfer, and Placental Pathology in Pregnancies During the COVID-19 Pandemic. JAMA Netw Open. 2020;3(12):e2030455. doi: https://doi.org/10.1001/jamanetworkopen.2020.30455
    | |
  9. Corbetta-Rastelli CM, Altendahl M, Gasper C, Goldstein JD, Afshar Y, Gaw SL. Analysis of placental pathology after COVID-19 by timing and severity of infection. Am J Obstet Gynecol MFM. 2023;5(7):100981. doi: https://doi.org/10.1016/j.ajogmf.2023.100981
    | |
  10. Abu-Dief EE, Elsayed HM, Atia EW, Abdel-Rahman M, Fawzy M. Modulation of Telocytes in Women with Preeclampsia: A Prospective Comparative Study. J Microsc Ultrastruct. 2021;9(4):158-63. doi: https://doi.org/10.4103/JMAU.JMAU_52_20
    | |
  11. Bosco C, Díaz E. Presence of Telocytes in a Non-innervated Organ: The Placenta. Adv Exp Med Biol. 2016;913:149-61. doi: https://doi.org/10.1007/978-981-10-1061-3_10
    | |
  12. Erkan E, Alptekin I, Serdaroglu B, Cetinkaya SE, Dastouri M, Celikkan FT, et al. Identification and localization of telocyte-like cells in human umbilical cord stroma. Sci Rep. 2025;15(1):39101. doi: https://doi.org/10.1038/s41598-025-26282-9
    | |
  13. Hashizume M, Gonzalez G, Ono C, Takashima A, Iwasaki M. Population-Specific ACE2 Single-Nucleotide Polymorphisms Have Limited Impact on SARS-CoV-2 Infectivity In Vitro. Viruses. 2021;13(1):67. doi: https://doi.org/10.3390/v13010067
    | |
  14. Garg R, Agarwal R, Yadav D, Singh S, Kumar H, Bhardwaj R. Histopathological Changes in Placenta of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Infection and Maternal and Perinatal Outcome in COVID-19. J Obstet Gynaecol India. 2023;73(1):44-50. doi: https://doi.org/10.1007/s13224-022-01666-3
    | |
  15. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8. doi: https://doi.org/10.1016/j.cell.2020.02.052
    | |
  16. Trinh IV, Desai SP, Ley SH, Mo Z, Satou R, Pridjian GC, et al. Prenatal Infection by Respiratory Viruses Is Associated with Immunoinflammatory Responses in the Fetus. Am J Respir Crit Care Med. 2024;209(6):693-702. doi: https://doi.org/10.1164/rccm.202308-1461OC
    | |
  17. Khoiwal K, Ravi AK, Mittal A, Pallapothu B, Priyadarshi M, Gaurav A, et al. Maternal-Fetal Characteristics of Pregnant Women With Severe COVID Disease and Maternal-Neonatal Characteristics of Neonates With Early-Onset SARS-CoV-2 Infection: A Prospective Data Analysis. Cureus. 2022;14(8):e27995. doi: https://doi.org/10.7759/cureus.27995
    |
  18. Turyanytsya SМ, Korchinska OO, Sabova АV, Baloga OА, Petrov VO. [Influence of SARS-CoV-2 acute respiratory viral disease on pregnancy and childbirth]. Reproductive health of woman. 2021;(2):15-8. Ukrainian. doi: https://doi.org/10.30841/2708-8731.2.2021.232515
    |
  19. Nagashima S, Mendes MC, Camargo Martins AP, Borges NH, Godoy TM, Miggiolaro A, et al. Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report. Arterioscler Thromb Vasc Biol. 2020;40(10):2404-7. doi: https://doi.org/10.1161/ATVBAHA.120.314860
    | |
  20. Jaiman S, Romero R, Pacora P, Jung EJ, Kacerovsky M, Bhatti G, et al. Placental delayed villous maturation is associated with evidence of chronic fetal hypoxia. J Perinat Med. 2020;48(5):516-8. doi: https://doi.org/10.1515/jpm-2020-0014
    | |
  21. Baergen RN, Heller DS. Placental Pathology in Covid-19 Positive Mothers: Preliminary Findings. Pediatr Dev Pathol. 2020;23(3):177-80. doi: https://doi.org/10.1177/1093526620925569
    | |
  22. Hecht JL, Quade B, Deshpande V, Mino-Kenudson M, Ting DT, Desai N, et al. SARS-CoV-2 can infect the placenta and is not associated with specific placental histopathology: a series of 19 placentas from COVID-19-positive mothers. Mod Pathol. 2020;33(11):2092-103. doi: https://doi.org/10.1038/s41379-020-0639-4
    | |
  23. Patanè L, Morotti D, Giunta MR, Sigismondi C, Piccoli MG, Frigerio L, et al. Vertical transmission of coronavirus disease 2019: severe acute respiratory syndrome coronavirus 2 RNA on the fetal side of the placenta in pregnancies with coronavirus disease 2019-positive mothers and neonates at birth. Am J Obstet Gynecol MFM. 2020;2(3):100145. doi: https://doi.org/10.1016/j.ajogmf.2020.100145
    | |
  24. Schwartz DA. An Analysis of 38 Pregnant Women With COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes. Arch Pathol Lab Med. 2020;144(7):799-805. doi: https://doi.org/10.5858/arpa.2020-0901-SA
    | |
  25. Kotlyar AM, Grechukhina O, Chen A, Popkhadze S, Grimshaw A, Tal O, et al. Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis. Am J Obstet Gynecol. 2021;224(1):35-53.e3. doi: https://doi.org/10.1016/j.ajog.2020.07.049
    | |
  26. Algarroba GN, Rekawek P, Vahanian SA, Khullar P, Palaia T, Peltier MR, et al. Visualization of severe acute respiratory syndrome coronavirus 2 invading the human placenta using electron microscopy. Am J Obstet Gynecol. 2020;223(2):275-8. doi: https://doi.org/10.1016/j.ajog.2020.05.023
    | |
  27. Wardhana MP, Kuntaman K, Utomo B, Aryananda RA, Rifdah SN, Wafa IA, et al. Evidence of Placental Villous Inflammation and Apoptosis in Third-Trimester Symptomatic SARS-CoV-2 Maternal Infection. Yonsei Med J. 2024;65(4):202-9. doi: https://doi.org/10.3349/ymj.2023.0309
    | |
  28. Giordano G, Petrolini C, Corradini E, Campanini N, Esposito S, Perrone S. COVID-19 in pregnancy: placental pathological patterns and effect on perinatal outcome in five cases. Diagn Pathol. 2021;16(1):88. doi: https://doi.org/10.1186/s13000-021-01148-6
    | |
  29. Savchuk T. [Pathomorphological changes of the placenta in the acute period of COVID-19 in pregnant women]. Eastern Ukrainian Medical Journal. 2024;12(2):323-34. Ukrainian. doi: https://doi.org/10.21272/eumj.2024;12(2):323-334
  30. Kramar S, Nebesna Z, Yakymchuk Y, Boychuk A, Shevchuk O, Korda M, et al. Changes in Placentas of Pregnant Women Infected with COVID-19. Int J Mol Sci. 2025;26(17):8596. doi: https://doi.org/10.3390/ijms26178596
    | |
  31. Agarwal N, Garg R, Singh S, Agrawal A. Coronavirus disease 2019 in pregnancy: Maternal and perinatal outcome. J Educ Health Promot. 2021;10(1):194. doi: https://doi.org/10.4103/jehp.jehp_954_20
    | |
  32. Smithgall MC, Liu-Jarin X, Hamele-Bena D, Cimic A, Mourad M, Debelenko L, et al. Third-trimester placentas of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive women: histomorphology, including viral immunohistochemistry and in-situ hybridization. Histopathology. 2020;77(6):994-9. doi: https://doi.org/10.1111/his.14215
    | |
  33. Savchuk T. Pathomorphological changes of the placenta in coronavirus disease (COVID-19) in pregnant women at 19-32 weeks of gestation. Proceeding of the Shevchenko Scientific Society. Medical Sciences. 2024;73(1). doi: https://doi.org/10.25040/ntsh2024.01.16
  34. Parcial A, Salomão NG, Portari EA, Arruda LV, de Carvalho JJ, de Matos Guedes HL, et al. SARS-CoV-2 Is Persistent in Placenta and Causes Macroscopic, Histopathological, and Ultrastructural Changes. Viruses. 2022;14(9):1885. doi: https://doi.org/10.3390/v14091885
    | |
  35. Husen MF, van der Meeren LE, Verdijk RM, Fraaij P, van der Eijk AA, Koopmans M, et al. Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms. Viruses. 2021;13(8):1670. doi: https://doi.org/10.3390/v13081670
    | |
  36. Pulinx B, Kieffer D, Michiels I, Petermans S, Strybol D, Delvaux S, et al. Vertical transmission of SARS-CoV-2 infection and preterm birth. Eur J Clin Microbiol Infect Dis. 2020;39(12):2441-5. doi: https://doi.org/10.1007/s10096-020-03964-y
    | |
  37. Khalel Al-Allaf LI, Al-Nauimi H. Histological changes of placenta in women with covid-19. Military Medical Science Letters. 2023;93(1):49-59. doi: https://doi.org/10.31482/mmsl.2023.005
  38. Savchuk TV, Leshchenko IV, Vaslovych VV, Chernenko OH, Malysheva TA. [Coronavirus disease 2019 (COVID-19) in pregnancy: pathomorphological ultrastructural changes of the placenta]. Pathologia. 2025;22(3):187-99. Ukrainian. doi: https://doi.org/10.14739/2310-1237.2025.3.338824
    |
  39. Horii M, To C, Morey R, Jacobs MB, Li Y, Nelson KK, et al. Histopathologic and Transcriptomic Profiling Identifies Novel Trophoblast Defects in Patients With Preeclampsia and Maternal Vascular Malperfusion. Mod Pathol. 2023;36(2):100035. doi: https://doi.org/10.1016/j.modpat.2022.100035
    | |
  40. Bryce C, Grimes Z, Pujadas E, Ahuja S, Beasley MB, Albrecht R, et al. Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience. Mod Pathol. 2021;34(8):1456-67. doi: https://doi.org/10.1038/s41379-021-00793-y
    | |
  41. Jaiswal N, Puri M, Agarwal K, Singh S, Yadav R, Tiwary N, et al. COVID-19 as an independent risk factor for subclinical placental dysfunction. Eur J Obstet Gynecol Reprod Biol. 2021;259:7-11. doi: https://doi.org/10.1016/j.ejogrb.2021.01.049
    | |
  42. Palomo M, Youssef L, Ramos A, Torramade-Moix S, Moreno-Castaño AB, Martinez-Sanchez J, et al. Differences and similarities in endothelial and angiogenic profiles of preeclampsia and COVID-19 in pregnancy. Am J Obstet Gynecol. 2022;227(2):277.e1-277.e16. doi: https://doi.org/10.1016/j.ajog.2022.03.048
    | |
  43. Naeh A, Berezowsky A, Yudin MH, Dhalla IA, Berger H. Preeclampsia-Like Syndrome in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19). J Obstet Gynaecol Can. 2022;44(2):193-5. doi: https://doi.org/10.1016/j.jogc.2021.09.015
    | |
  44. Serrano B, Bonacina E, Garcia-Ruiz I, Mendoza M, Garcia-Manau P, Garcia-Aguilar P, et al. Confirmation of preeclampsia-like syndrome induced by severe COVID-19: an observational study. Am J Obstet Gynecol MFM. 2023;5(1):100760. doi: https://doi.org/10.1016/j.ajogmf.2022.100760
    | |

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Published

2026-06-09

How to Cite

Savchuk, T. V., & Leshchenko, I. V. (2026). Pathomorphological ultrastructural changes in the placenta in coronavirus disease 2019 (COVID-19) during pregnancy: a literature review. Modern Medical Technology, 18(2), 135–139. https://doi.org/10.14739/mmt.2026.2.344103

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Vol. 18 No. 2 (2026)

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Reviews of literature

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Copyright (c) 2026 T. V. Savchuk, I. V. Leshchenko

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