COVID-19 and pregnancy: impact, outcomes, and potential therapy
V. I. Shcherbakov, 
T. I. Ryabichenko,
O. O. Obukhova,
T. V. Kartseva,
V. E. Menshchikova,
D. V. Eliseeva,
M. I. Voevoda
T. I. Ryabichenko,
O. O. Obukhova,
T. V. Kartseva,
V. E. Menshchikova,
D. V. Eliseeva,
M. I. Voevoda https://doi.org/10.18699/SSMJ20240406
Abstract
The impact of the new coronavirus COVID-19 infection on the course of pregnancy, maternal and child health is largely unclear and controversial. The presented literature review analyzes changes in the immune, cardiovascular, and endocrine systems in women in physiological pregnancy. The peculiarities of the course of infection caused by SARS-CoV-2 virus in pregnancy, depending on the virus variant, are presented, the issues of infection pathways into immune and non-immune cells, including placental cells, as well as the issues of transplacental transfer of the virus – the key moment of infection of the embryo or fetus, on which the outcome of pregnancy also largely depends, are considered. Promising approaches to COVID-19 therapy are presented: use of inhibitors of transmembrane serine protease 2 (TMPRSS2), furin, angiotensin-converting enzyme (ACE2) and RNA-dependent RNA polymerase, amnion epithelial cells and their exosomes. At the same time, the potential use of mesenchymal stem cells in patients with severe COVID-19 pneumonia is reviewed. Difficulties and questions regarding the use of the above therapeutic methods in pregnant women are highlighted. Aspects of the use of surfactant preparations in newborns at risk of new coronavirus infection are considered.
About the Authors
V. I. Shcherbakov
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Vladimir I. Shcherbakov, doctor of medical science
630117, Novosibirsk, Timakova st., 2
T. I. Ryabichenko
Federal Research Center of Fundamental and Translational Medicine; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
Tatyana I. Ryabichenko, doctor of medical science
630117, Novosibirsk, Timakova st., 2
630091, Novosibirsk, Krasny ave., 52
O. O. Obukhova
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Olga O. Obukhova, doctor of medical science
630117, Novosibirsk, Timakova st., 2
T. V. Kartseva
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
Tatyana V. Kartseva, doctor of medical science
630091, Novosibirsk, Krasny ave., 52
V. E. Menshchikova
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
Valeria E. Menshchikova
630091, Novosibirsk, Krasny ave., 52
D. V. Eliseeva
Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation
Russian Federation
Daria V. Eliseeva
630091, Novosibirsk, Krasny ave., 52
M. I. Voevoda
Federal Research Center of Fundamental and Translational Medicine
Russian Federation
Russian Federation
Mikhail I. Voevoda, doctor of medical science, professor, academician of the RAS
630117, Novosibirsk, Timakova st., 2
References
1. Kravtsova O.N., Vishnevskaya A.V., Chernov K.G. Coronavirus and pregnancy. Mezhdunarodnyy nauchno-issledovatel’skiy zhurnal = International Research Journal. 2022;(11):52–54. [in Russian]. doi: 10.23670/ IRJ.2022.125.39
2. Adamyan L.V., Vechorko V.I., Konysheva O.V., Kharchenko E.I. Pregnancy and COVID-19: current issues (literature review). Problemy reproduktsii = Russian Journal of Human Reproduction. 2021;27(3):70– 77. [In Russian]. doi: 10.17I16/repro20212703170
3. Kosolapova Yu.A., Morozov L.A., Inviyaeva E.V., Makieva M.I., Zubkov V.V., Degtyarev D.N. Impact of COVID-19 on pregnancy outcomes and neonatal health (literature review). Akusherstvo i ginekologiya. Novosti. Mneniya. Obucheniye = Obstetrics and Gynecology. News. Opinions. Training. 2021;9(4):63–70. [In Russian]. doi: 10.33029/2303-9698-2021-9-4-63-70
4. Poon L.C., Yang H., Lee J.C., Copel J.A., Leung T.Y., Zhang Y., Chen D., Prefumo F. ISUOG Interim Guidance on 2019 novel coronavirus infection during pregnancy and puerperium: information for healthcare professionals. Ultrasound Obstet. Gynecol. 2020;5(5): 700–708. doi: 10.1002/uog.22013
5. Chen R., Zhang S., Su S., Ye H., Shu H. Interactions between specific immune status of pregnant women and SARS-CoV-2 infection. Front. Cell. Infect. Microbiol. 2021;11:721309. doi: 10.3389/fcimb.2021.721309
6. Lampé R., Kövér Á., Szűcs S., Pál L., Árnyas E., Ádány R., Póka R. Phagocytic index of neutrophil granulocytes and monocytes in healty and preeclamptic pregnancy. J. Reprod. Immunol. 2015;107:26–30. doi: 10.1016/j.jri.2014.11.001
7. Hennighausen L., Lee H.K. Aktivation of the SARS-CoV-2 receptor ACE2 through JAK/ STAT-dependent enhancers during pregnancy. Cell Rep. 2020;32(13):108–199. doi: 10.1016/j.celrep.2020.108199
8. Saadedine M., El Sabeh M., Borahay M.A., Daoud G. The influence of COVID-19 infection-associated immune response on the female reproductive system. Biol. Reprod. 2023;108(2):172–182. doi: 10.1093/ biolre/ioac187
9. Carvajal J., Casanello P., Toso A., Farias M., Carrasco-Negue K., Araujo K., Valero P., Fuenzalida J., Solari C., Sobrevia L. Functional conseguences of SARS- Cov-2 infection in pregnant women fetoplacental unit, and neonate. Biochim. Biophys. Acta Mol. Basis Dis. 2023;1869(1):166582. doi: 10.1016/j.bbadis.2022.166582
10. Volz E., Hill V., McCrone J.T., Price A., Jorgensen D., O’Toole Á., Southgati J., Johnson R., Jackson B., Nascimento F.F., … Connor T.R. Evaluating the effects of SARS-CoV-2 spikemutation D 614 G on transmis-sibility and pathogenicity. Cell. 2021;184(1):64–75. doi: 10.1016/j.cell.2020.11.020
11. Takeda M. Proteolytic activation of SARS-CoV-2 spike protein. Microbiol. Immunol. 2022;66(1):15–23. doi: 10.1111/1348-0421.12945
12. Becerra-Flores M., Cardozo T. SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate. Int. J. Clin. Pract. 2020;74(8):13525. doi: 10.1111/ijcp.13525
13. da Cunha Sobieray N.L.E., Zanela M., Padilha S.L., Klas C.F., de Carvalho N.S. HELLP-syndrome and COVID-19:A minor revision of a possible new “COVID-19-linked HELLP-like syndrome”. Eur. J. Obstet. Gynecol. Reprod. Biol. 2023;283:90–94. doi: 10.1016/j.ejogrb.2023.02.005
14. Warning J.C., McCracken S.A., Morris J.M. A balancing act:mechanism by which the fetus avoids rejection by the maternal immune system. Reproduction. 2011;141(6):715–724. doi: 10.1530/REP-10-0360
15. Mizumoto K., Kagaya K., Zarebski A., Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020 [published correction appears in Euro Surveill. 2020 Jun;25(22):]. Euro Surveill. 2020;25(10):2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180
16. Chen L., Qu I., Kalyani F.S., Zhand Q., Fan L., Fand Y., Li Y., Xiand C. Mesenchymal stem cell – based treatments for COVID-19: status and future perspectives for clinical applications. Cell. Mol. Life Sci. 2022;79(3):142. doi: 10.1007/s00018-021-04096-y
17. Piazza G., Morrow D.A. Diagnosis, management and pathophysiology of arterial and venous thrombosis in COVID-19. IAMA. 2020;324(24):2548–2549. doi: 10.1001/jama.2020.23422
18. Hariri L.P., North C.M., Shih A.K., Israel R.A., Maley J.H., Villalba J.A.,Vinarsky V., Rubin I., Okin D.A., Schafani A., … Mino-Kenudson M. Lung histopathology in corona virus discase 2019 as compared with severe aclite respiratory syndrome and H1N1 influenza: a systematic review. Chest. 2021;159(1):73– 84. doi: 10.1016/j.chest.2020.09.259
19. Ouyang Y., Bagalkot T., Fitzgerald W., Sadovsky E., Chu T., Martinez-Marchal A., Briefio-Enriguez M., Su E.J., Margolis L., Sorkin A., Sadovsky Y. Term human placental trophoblasts express SARS-CoV-2 entry factors ACE2, TMPRSS2, and Furin. mSphere. 2021;6(2):e00250–21. doi: 10.1128/mSphere.00250-21
20. Montano M., Victor A.R., Griffin D.K., Duong T., Bolduc N., Farmer A., Gard V., Hadjantonakis A.K., Coates A., Barnes F.I., Zouves C.G., Greene W.C., Viotti M. SARS-CoV-2 can infect human embryos. Sci. Rep. 2022;12(2):15451. doi: 10.1038/s41598-022-18906-1
21. Robson A., Harris L.K., Innes B.A., Lash P.N., Aljunaidy M.M., Aplin J.D., Baker P.N., Robson S.C., Bulmer J.J. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB J. 2012;26(12):4876–4885. doi: 10.1096/fj-12-210310
22. Al-Rawaf S.A., Mousa E.T., Kareem N.M. Correlation between pregnancy outcome and placental pathology in COVID-19 pregnant women. Infect. Dis. Obstet. Gynecol. 2022;2022:8061112. doi: 10.1155/2022/8061112
23. Joshi B., Chandi A., Srinivasan R., Saini S.S., Prasad G.R.V., Puri G.D., Bhalla A., Suri V., Bagga R. The placental pathology in Coronavirus disease 2019 infected mothers and its impact on pregnancy outcome. Placenta. 2022;127:1–7. doi: 10.1016/j.placenta.2022.07.009
24. Juttukonda L.J., Wachma E.M., Boateng J., Jain M., Benarroch Y., Taglauer E.S. Decidual immune response following COVID-19 during pregnancy varies by timing of maternal SARS-CoV-2 infection. J. Reprod. Immunol. 2022;151:103501. doi: 10.1016/ j.jri.2022.103501
25. Abate B.B., Kassie A.V., Kassaw M.W., Aragie T.G., Masresha S.A. Sex difference in coronavirus disease (COVID-19): a systematic rewiew and meta-analysis. BMJ Open. 2020;10(10):e040129. doi: 10.1136/bmjopen-2020-040129
26. Yang Y., Xing H., Zhao Y. Transphlacental transmission of SARS-CoV-2 immunoglobulin G antibody to infants from maternal COVID-19 vaccine immune zation before pregnancy. J. Med. Virol. 2023;95(1):e28296. doi: 10/1002/jmv.28296
27. Essalmani R., Jain J., Susan-Resiga D., Andreo U., Evagelidis A., Derbali R.M., Huynh D.N., Dallaire F., Laporte M., Delpal A., … Seidah N.G. Distinctive roles of furin and TMPRSS2 in SARS-CoV-2 infectivity. J. Med. Virol. 2022;96(8):e00128–22. doi: 10.1128/jvi.00128-22
28. Agostinis C., Toffoli M., Spazzapan M., Balduit A., Zito G., Mangogna A., Zupin L., Salviato T., Maiocchi S., Romano F., … Bulla R. SARS-CoV-2 modulates virus receptor expression in placenta and can induce trophoblast fusion, inflammation and endothelial permeability. Front. Immunol. 2022;13(13):957224. doi: 10.3389/fimmu.2022.957224
29. Trbojević-Akmačić I., Petrović T., Lauc G. SARS-CoV-2 S glycoprotein binding to multiple host receptors enables cell entry and infection. Glycoconj J. 2021;38(5):611–623. doi: 10.1007/s10719-021-10021-z
30. Matveeva O., Nechipurenko Y., Lagutkin D., Yegorov Y.E., Kzhyshkowska J. SARS-CoV-2 infection of phagocytic immune cells and COVID-19 pathology: Antibody-dependent as well as independent cell entry. Front. Immunol. 2022;13:1050478. doi: 10.3389/fimmu.2022.1050478
31. Ajmeriya S., Kumar A., Karmakar S., Rana S., Singh H. Neutralizing antibodies and antibody-depenaent enhancement in COVID-19: perspective. J. Indian Inst. Sci. 2022;102(2):671–687. doi: 10.1007/s41745-021-00268-8
32. Liu Y., Arase H. Neutralizing and enhancing antibodies against SARS-CoV-2. Inflamm Regen. 2022;5;42(1):58. doi: 10.1186/s41232-022-00233-7
33. Hoffmann M., Kleinc-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., Müller M.A., Drosten C., Pöhlmann S. 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. doi: 10.1016/j.cele.2020.02.052
34. Chaube U., Patel B.D., Bhatt H.G. A hypottesis on designing strategy of effective RdRp inhibitors for the treatment of SARS-CoV-2. 3 Biotech. 2023;13(1):12. doi: 10.1007/s13205-022-03430-w
35. Babajani A., Moeinabadi-Bidgoli K., Niknejad F., Rismanchi H., Shafiee S., Shariatzadeh S., Jamshidi E., Farjoo M.H., Niknejad H. Human placentaderived amniotic epithelial cells as a new therapeutic hope for COVID-19-associated acute respiratory distress syndrome (ARDS) and systemic inflammation. Stem. Cell. Res. Ther. 2022;13(1):126. doi: 10.1186/s13287-022-02794-3
36. Hodges R.J., Jenkin G., Hooper S.B., Allison B., Lim R., Dickinson H., Miller S.L., Vosdoganes P., Wallace E.M. Human amnion epithelial cells reduce ventilation-induced preterm lung injuery in fetal shep. Am. J. Obstet. Gynecol. 2012;206(5):448. doi: 10.1016/j.ajog.2012.02.038
37. Tan J.L., Lau S.N., Leaw B., Nguyen H.P.T., Salamonsen L.A., Saad M.I., Chan S.T., Zhu D., Krause M., Kim C., Sievert W., Wallace E.M., Lim R. Amnion epithelial cell-derived exosomes restrict lung injury and enhance endogenous lung repair. Stem. Cells Transl. Med. 2018;7(2):180–196. doi: 10.1002/sctm.17-0185
38. Stock S.J., Kelly R.W., Riley S.C., Calder A.A. Natural antimicrobial production by the amnion. Am. J. Obstet. Gynecol. 2007;196(3):255. doi: 10.1016/j.ajog.2006.10.908
39. Guo Z., Chen Y., Luo X., He X., Zhang Y., Wang J. Administration of umbilical cord mesenchymal stem cells in patients with severe COVID-19 pneumonia. Crit Care. 2020;24(1):420. doi: 10.1186/s13054-020-03142-8
40. Karakaş N., Üçüncüoğlu S., Uludağ D., Karaoğlan B.S., Shah K., Öztürk G. Mesenchymal stem cell-based COVID-19 therapy: bioengineering perspectives. Cells. 2022;11(3):465. doi: 10.3390/cells11030465
41. Sengupta V., Sengupta S., Lazo A., Woods P., Nolan A., Bremer N. Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem. Cells Dev. 2020;29(12):747–754. doi: 10.1089/scd.2020.0080
42. Javed A., Karki S., Somi Z ., Khan Z., Shree A., Sah B.K., Ghosh S., Saxena S. Association between mesenchymal stem cells and COVID 19 therapy: systematic review ana current thrends. Biomed. Res. Int. 2022;2022:9346939. doi: 10.1155/2022/9346939
43. Chen L., Qu I., Kalyani F.S., Zhand Q., Fan L., Fand Y., Li Y., Xiand C. Mesenchymal stem cell – based treatments for COVID-19: status and future perspectives for clinical applications. Cell. Mol. Life Sci. 2022;79(3):142. doi: 10.1007/s00018-021-04096-y
44. Sheinin M., Jeong B., Puidi R.K., Pahan K. Regression of lung cancer in mice by intranasal administration of SARS-CoV-2 spike S1. Cancers (Basel). 2022;14(22):5648. doi: 10.3390/cancers14225648
Review
For citations:
Shcherbakov V.I., Ryabichenko T.I., Obukhova O.O., Kartseva T.V., Menshchikova V.E., Eliseeva D.V., Voevoda M.I. COVID-19 and pregnancy: impact, outcomes, and potential therapy. Сибирский научный медицинский журнал. 2024;44(4):62-70. (In Russ.) https://doi.org/10.18699/SSMJ20240406
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