Clinical and genetic determinants of severe course of COVID-19 in pregnant women




COVID-19, pregnancy, hemostasis system, inflammatory markers, genetic markers


Objectives: to determine the clinical and genetic determinants of the severe course of COVID-19 in pregnant women in order to identify a risk group and search for therapeutic targets.
Materials and methods. 21 patients (group 1) with a severe course of COVID-19 who required intensive care in the Anesthesiology and Intensive Care Unit (AICU) and 126 pregnant women with moderate severity treated in the Infectious-Obstetrics Unit (IOCU) were examined (group 2). Genomic DNA for molecular genetic analysis of gene variants ACE (I/D, rs 4340), PGR (Alu insertion), ESR1 (A351G, rs 9340799), PON1 (C108T, rs 705379) was isolated from the peripheral blood of patients using a commercial Quick-DNA Miniprep Plus Kit (Zymo Research, USA). Variants of ACE and PGR genes were determined using allele-specific polymerase chain reaction; polymerase chain reaction followed by restriction analysis was used to determine ESR1 and PON1 gene variants.
Results. Severe course of COVID-19 is observed in 18.2% of pregnant women, critical condition in 7.5%. A third of AICU patients are over 35 years old. Somatic anamnesis was complicated in 23.8% of patients; thyroid gland pathology (14.3%) and varicose disease (19.0%) prevailed. A significant factor in the severe course of COVID-19 is obesity of the III–IV degree in 28.5% cases. The severe course of the disease was associated with complications of pregnancy (oligohydramnios – 52.4%, ahydramnios – 14.3%, fetal growth retardation syndrome – 33.3%, circulatory disorders – 57.1%, fetal distress – 47.6%, preeclampsia – 14.3%), labor (caesarean section – 57.1%, premature birth – 28.6%), disorders of newborns state (asphyxia – 35.6%). These patients are characterized by anemia (58.7%), thrombocytopenia (23.8%), leukocytosis (33.3%), lymphopenia (90.5%), a shift of the leukocyte formula to the left (an increase of rod-nuclear leukocytes by 85.7%). There were significantly increased levels of transaminases: alanine aminotransferase in 47.6%, aspartate aminotransferase in 76.2%. Prothrombotic changes are indicated by a decrease in prothrombin time and activated partial thromboplastin time in 66.7%, which is confirmed by an increase in D-dimer in 85.7% of patients up to the maximum 15,000 ng/ml in 9.5% of women. An increase in inflammation markers (C-reactive protein and interleukin-6 in all AICU patients, procalcitonin in 66.7%) is a reflection of the destructive effect of inflammatory processes. The genetic determinants of the severe course of COVID-19 in pregnant women can be the ID genotype of the ACE I/D rs4340 polymorphism (81.0%), the T2/T2 PROGINS genotype (19.0%), the ESR1 A351G rs9340799 GG genotype (28.5%).
Conclusions. The use of separate clinical, laboratory and genetic indicators in pregnant women with COVID-19 will contribute to the selection of the risk group of a coronavirus severe course and the determination of targets of therapeutic impact.

Author Biographies

V.V. Kaminskyi, P.L. Shupyk National Healthcare University of Ukraine, Kyiv

Academician of the NAMS of Ukraine, MD, professor, chief of the Department of Obstetrics, Gynecology and Reproductology

L.I. Vorobei, .L. Shupyk National Healthcare University of Ukraine, Kyiv

Associate professor, Department of Obstetrics, Gynecology and Reproductology

O.I. Zhdanovych, P.L. Shupyk National Healthcare University of Ukraine, Kyiv

MD, professor, Neonatology Department

S.M. Korniienko, Odesa National Medical University, Odesa

MD, professor, Department of Obstetrics and Gynecology

T.V. Kolomiichenko, .L. Shupyk National Healthcare University of Ukraine, Kyiv

PhD, chief researcher, Department of Obstetrics, Gynecology and Reproductology

О.Р. Fastovets, Kyiv City Center of Reproductive and Perinatal Medicine, Kyiv



  1. Aho Glele, L.S., Simon, E., Bouit, C., et al. “Association between SARS-Cov-2 infection during pregnancy and adverse pregnancy outcomes: A re-analysis of the data reported by Wei et al. (2021).” Infect Dis Now 52.3 (2022): 123–8. DOI: 10.1016/j.idnow.2022.02.009
  2. Akbari, M., Taheri, M., Mehrpoor, G., et al. “Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients.” Vascul Pharmacol 142 (2022): 106934. DOI: 10.1016/j.vph.2021.106934
  3. The New York Times. Coronavirus World Map: Tracking the Global Outbreak. Available from: [], last accessed 20 July, 2022.
  4. de Medeiros, K.S., Sarmento, A.C.A., Costa, A.P.F., et al. “Consequences and implications of the coronavirus disease (COVID-19) on pregnancy and newborns: A comprehensive systematic review and meta-analysis.” Int J Gynaecol Obstet 156.3 (2022): 394–405. DOI: 10.1002/ijgo.14015
  5. Decharatchakul, N., Settasatian, C., Settasatian, N., et al. “Association of combined genetic variations in SOD3, GPX3, PON1, and GSTT1 with hypertension and severity of coronary artery disease.” Heart Vessels 35.7 (2020): 918–29. DOI: 10.1007/s00380-020-01564-6
  6. Diels, S., Cuypers, B., Tvarijonaviciute, A., et al. “A targeted multi-omics approach reveals paraoxonase-1 as a determinant of obesity-associated fatty liver disease.” Clin Epigenetics 13.1 (2021): 158. DOI: 10.1186/s13148-021-01142-1
  7. Emeruwa, U.N., Gyamfi-Bannerman, C., Miller, R.S. “Health Care Disparities in the COVID-19 Pandemic in the United States: A Focus on Obstetrics.” Clin Obstet Gynecol 65.1 (2022): 123–33. DOI: 10.1097/GRF.0000000000000665
  8. Fishchuk, L.Y. “Association of genotypes by polymorphic variant C-108T of PON1 gene with the risk of developing breast cancer and hypertensive disease in women.” Biopolymers and Cell 30.4 (2014): 310–3. DOI: 10.7124/bc.0008A6
  9. Fishchuk, L.E., Gorovenko, N.G. “Genetic polymorphisms of the renin-angiotensin system in breast cancer patients.” Exp Oncol 35.2 (2013): 101–4. 23828384
  10. Kaminskyi, V., Tkachenko, R., Kaminskyi, A., et al. “Therapeutic Opportunities for Improving the Course of Coronavirus Disease and Reducing the Frequency of Gestional Complications.” Reproductive Endocrinology 62 (2021): 8–13. DOI: 10.18370/2309-4117.2021.62.8-13
  11. Kornatska, A.G., Flaksemberg, М.А., Chubei, G.V., et al. “Progins (T2) variant of the PGR gene may reduce the ESR1 gene-dependent risk of uterine leiomyoma development.” World Med Biol 2 (2021): 58–63. DOI: 10.26724/2079-8334-2021-2-76-58-63
  12. Li, M., Schifanella, L., Larsen, P.A. “Alu retrotransposons and COVID-19 susceptibility and morbidity.” Hum Genomics 15.1 (2021): 2. DOI: 10.1186/s40246-020-00299-9
  13. Lippi, G., Plebani, M. “Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis.” Clin Chim Acta 505 (2020): 190–1. DOI: 10.1016/j.cca.2020.03.004
  14. Mehta, P., McAuley, D.F., Brown, M., et al. “COVID-19: consider cytokine storm syndromes and immunosuppression.” Lancet (London, England) 395.10229 (2020): 1033–4. DOI: 10.1016/S0140-6736(20)30628-0
  15. Paliychuk, O.V., Polishchuk, L.Z., Rossokha, Z.I., Chekhun, V.F.“Molecular-genetic models for prognosis of development of tumors of reproductive system in women with family history of cancer.” Exp Oncol 40.1 (2018): 59–67.
  16. Parker, M.G., Arbuckle, N., Dauvois, S., et al. “Structure and function of the estrogen receptor.” Ann N Y Acad Sci 684 (1993): 119–26. DOI: 10.1111/j.1749-6632.1993.tb32276.x
  17. Pati, A., Mahto, H., Padhi, S., Panda, A.K. “ACE deletion allele is associated with susceptibility to SARS-CoV-2 infection and mortality rate: An epidemiological study in the Asian population.” Clin Chim Acta 510 (2020): 455–8. DOI: 10.1016/j.cca.2020.08.008
  18. Ponti, G., Maccaferri, M., Ruini, C., et al. “Biomarkers associated with COVID-19 disease progression.” Crit Rev Clin Lab Sci 57.6 (2020): 389–99. DOI: 10.1080/10408363.2020.1770685
  19. Popkin, B.M., Du, S., Green, W.D., et al. “Individuals with obesity and COVID-19: A global perspective on the epidemiology and biological relationships.” Obes Rev 21.11 (2020): e13128. DOI: 10.1111/obr.13128
  20. Rangchaikul, P., Venketaraman, V. “SARS-CoV-2 and the Immune Response in Pregnancy with Delta Variant Considerations.” Infect Dis Rep 13.4 (2021): 993–1008. DOI: 10.3390/idr13040091
  21. Rossokha, Z.I., Fishchuk, L.Y., Pokhylko, V.I., et al. “The deletion variant of the CCR5 gene (rs333) but not the ACE gene (rs4340) is associated with long-term respiratory support in patients with COVID-19 pneumonia.” Ukrainian medical journal 6.2 (2020): 1–5. DOI: 10.32471/umj.1680-3051.140.196058
  22. Saengsiwaritt, W., Jittikoon, J., Chaikledkaew, U., Udomsinprasert, W. “Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID-19 severity: A systematic review with meta-analysis.” Rev Med Virol 32.4 (2022): e2323. DOI: 10.1002/rmv.2323
  23. Seasely, A.R., Blanchard, C.T., Arora, N., et al. “Maternal and Perinatal Outcomes Associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) Variant.” Obstet Gynecol 138.6 (2021): 842–4. DOI: 10.1097/AOG.0000000000004607
  24. Shi, Q., Wu, M., Chen, P., et al. “Criminal of Adverse Pregnant Outcomes: A Perspective From Thyroid Hormone Disturbance Caused by SARS-CoV-2.” Front Cell Infect Microbiol 11 (2022): 791654. DOI: 10.3389/fcimb.2021.791654
  25. Su, S., Hua, D., Li, J.-P., et al. “Modulation of innate immune response to viruses including SARS-CoV-2 by progesterone.” Signal Transduct Target Ther 7.1 (2022): 137. DOI: 10.1038/s41392-022-00981-5
  26. Tan, C., Huang, Y., Shi, F., et al. “C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early.” J Med Virol 92.7 (2020): 856–62. DOI: 10.1002/jmv.25871
  27. Terpos, E., Ntanasis-Stathopoulos, I., Elalamy, I., et al. “Hematological findings and complications of COVID-19.” Am J Hematol 95.7 (2020): 834–47. DOI: 10.1002/ajh.25829
  28. Zhao, G., Cai, Y., Liu, J, Meng, T. “Association between the estrogen receptor α gene polymorphisms rs2234693 and rs9340799 and severe and mild pre-eclampsia: a meta-analysis.” Biosci Rep 39.2 (2019): BSR20181548. DOI: 10.1042/BSR20181548
  29. Zheng, H., Cao, J.J. “Angiotensin-Converting Enzyme Gene Polymorphism and Severe Lung Injury in Patients with Coronavirus Disease 2019.” Am J Pathol 190.10 (2020): 2013–7. DOI: 10.1016/j.ajpath.2020.07.009



How to Cite

Kaminskyi, V., Vorobei, L., Zhdanovych, O., Korniienko, S., Kolomiichenko, T., & Fastovets О. (2022). Clinical and genetic determinants of severe course of COVID-19 in pregnant women. REPRODUCTIVE ENDOCRINOLOGY, (65), 38–43.



Pregnancy and childbirth