Pregnancy, Preeclampsia, and COVID-19: Susceptibility and Mechanisms: A Review Study

Document Type : Review Article

Authors

1 Infectious Diseases Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

2 Department of Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

3 Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran.

4 Behavioral Diseases Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through angiotensin converting enzyme  2 (ACE2), which expression of its gene increases during pregnancy that is resulted in an enhanced level of the ACE2  enzyme. It might enhance the risk of SARS-CoV-2 infection and its complications in the pregnant women. Although,  pregnancy hypertensive disorders and severe infection with SARS-CoV-2 are correlated with high comorbidity, these  two entities should be discriminated from each other. Also, there is a concern about the risk of preeclampsia and  consequently severe coronavirus disease 2019 (COVID-19) development in the pregnant women. So, to answer these  questions, in the present review the literature was surveyed. It seems there is higher severity of COVID-19 among  pregnant women than non-pregnant women and more adverse pregnancy outcomes among pregnant women infected  with SARS-CoV-2. In addition, an association between COVID-19 with preeclampsia and the role of preeclampsia  and gestational hypertension as risk factors for SARS-CoV-2 infection and its complications is suggested. However, infection of the placenta and the SARS-CoV-2 vertical transmission is rare. Various mechanisms could explain the role of COVID-19 in the risk of preeclampsia and association between preeclampsia and COVID-19. Suggested mechanisms are included decreased ACE2 activity and imbalance between Ang II and Ang-(1-7) in preeclampsia, association of both of severe forms of COVID-19 and pregnancy hypertensive disorders with comorbidity, and interaction between immune system, inflammatory cytokines and the renin angiotensin aldosterone system and its contribution to the hypertension pathogenesis. It is concluded that preeclampsia and gestational hypertension might be risk factors for SARS-CoV-2 infection and its complications.

Keywords


1. Ebrahimi A, Sayad B, Rahimi Z. COVID-19 and psoriasis: biologic treatment and challenges. J Dermatolog Treat. 2020: 1-5.
2. Touyz RM, Li H, Delles C. ACE2 the Janus-faced protein - from cardiovascular protection to severe acute respiratory syndrome-coronavirus and COVID-19. Clin Sci (Lond). 2020; 134(7): 747-750.
3. Skarstein Kolberg E. ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease. J Clin Virol. 2020; 126: 104350. 
4. Verma S, Carter EB, Mysorekar IU. SARS-CoV2 and pregnancy: an invisible enemy? Am J Reprod Immunol. 2020; 84(5): e13308. 
5. de Souza Silva GA, da Silva SP, da Costa MAS, da Silva AR, de Vasconcelos Alves RR, Ângelo Mendes Tenório FDC, et al. SARSCoV, MERS-CoV and SARS-CoV-2 infections in pregnancy and fetal development. J Gynecol Obstet Hum Reprod. 2020; 49(10): 101846.
6. Thomas B, Pallivalapila A, El Kassem W, Tarannum A, Al Hail F, Rijims M, et al. Maternal and perinatal outcomes and pharmacological management of Covid-19 infection in pregnancy: a systematic review protocol. Syst Rev. 2020; 9(1): 161.
7. Sinkey RG, Rajapreyar I, Robbins LS, Dionne-Odom J, Pogwizd SM, Casey BM, et al. Heart failure with preserved ejection fraction in a postpartum patient with superimposed preeclampsia and COVID-19. AJP Rep. 2020; 10(2): e165-e168.
8. Rahimi Z, Malek-Khosravi S, Rahimi Z, Jalilvand F, Parsian A. MTHFR C677T and eNOS G894T variants in preeclamptic women: contribution to lipid peroxidation and oxidative stress. Clin Biochem. 2013; 46(1-2): 143-147.
9. Lumbers ER, Delforce SJ, Arthurs AL, Pringle KG. Causes and consequences of the dysregulated maternal renin angiotensin system in preeclampsia. Front Endocrinol (Lausanne). 2019; 10: 563.
10. Rahimi Z. The role of renin angiotensin aldosterone system genes in diabetic nephropathy. Can J Diabetes. 2016; 40(2): 178-183.
11. Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, 
diabetic retinopathy and diabetic neuropathy. J Res Med Sci. 2014; 19(11): 1090-1098.
12. Kar M. Role of biomarkers in early detection of preeclampsia. J Clin Diagn Res. 2014; 8(4): BE01-4. 
13. Rahimi Z, Lotfi S, Ahmadi A, Jalilian N, Shakiba E, Vaisi-Raygani A, et al. Matrix metalloproteinase-2 C-735T and its interaction with matrix metalloproteinase-7 A-181G polymorphism are associated with the risk of preeclampsia: influence on total antioxidant capacity and blood pressure. J Obstet Gynaecol. 2018; 38(3): 327-332. 
14. Ueki N, Takeda S, Koya D, Kanasaki K. The relevance of the reninangiotensin system in the development of drugs to combat preeclampsia. Int J Endocrinol. 2015; 2015: 572713.
15. Rahimi Z, Rahimi Z, Mozafari H, Parsian A. Preeclampsia and angiotensin converting enzyme (ACE) I/D and angiotensin II type-1 receptor (AT1R) A1166C polymorphisms: association with ACE I/D 
polymorphism. J Renin Angiotensin Aldosterone Syst. 2013; 14(2): 174-180.
16. Kurlak LO, Williams PJ, Bulmer JN, Broughton Pipkin F, Mistry HD. Placental expression of adenosine A(2A) receptor and hypoxia inducible factor-1 alpha in early pregnancy, term and pre-eclamptic pregnancies: interactions with placental renin-angiotensin system. Placenta. 2015; 36(5): 611-613. 
17. Zhang AK. The potential participation of abdominal pressure in preeclampsia. Med Hypotheses. 2015; 84(6): 583-585. 
18. Świątkowska-Stodulska R, Kmieć P, Stefańska K, Sworczak K. Renin-angiotensin-aldosterone system in the pathogenesis of pregnancy-induced hypertension. Exp Clin Endocrinol Diabetes. 
2018; 126(6): 362-366.
19. Irani RA, Xia Y. Renin angiotensin signaling in normal pregnancy and preeclampsia. Semin Nephrol. 2011; 31(1): 47-58. 
20. Xue B, Zhang Y, Johnson AK. Interactions of the brain renin-angiotensin-system (RAS) and inflammation in the sensitization of hypertension. Front Neurosci. 2020; 14: 650.
21. Mendoza M, Garcia-Ruiz I, Maiz N, Rodo C, Garcia-Manau P, Serrano B, et al. Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study. BJOG. 2020; 127(11): 1374-1380.
22. Rolnik DL. Can COVID-19 in pregnancy cause pre-eclampsia? BJOG. 2020; 127(11): 1381.
23. Antoun L, Taweel NE, Ahmed I, Patni S, Honest H. Maternal COVID-19 infection, clinical characteristics, pregnancy, and neonatal outcome: a prospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2020; 252: 559-562. 
24. Dap M, Morel O. Proteinuria in Covid-19 pregnant women: preeclampsia or severe infection? Eur J Obstet Gynecol Reprod Biol. 2020; 252: 612. 
25. Papageorghiou AT, Deruelle P, Gunier RB, Rauch S, García-May PK, Mhatre M, et al. Preeclampsia and COVID-19: results from the INTERCOVID prospective longitudinal study. Am J Obstet Gynecol. 2021; 225(3): 289.e1-289.e17.
26. Allotey J, Stallings E, Bonet M, Yap M, Chatterjee S, Kew T, et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020; 370: m3320.
27. Di Mascio D, Khalil A, Saccone G, Rizzo G, Buca D, Liberati M, et al. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2020; 2(2): 100107.
28. Azarkish F, Sheikhi F, Mirkazehi Z, Kalkali S, Bameni Moghadam P, Zahirniya M. Preeclampsia and the crucial postpartum period for Covid-19 infected mothers: a case report. Pregnancy Hypertens. 2021; 23: 136-139. 
29. Hansen JN, Hine J, Strout TD. COVID-19 and preeclampsia with severe features at 34-weeks gestation. Am J Emerg Med. 2021; 39: 252.e3-252.e5. 
30. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395(10226): 809-815. 
31. Coronado-Arroyo JC, Concepción-Zavaleta MJ, Zavaleta-Gutiérrez FE, Concepción-Urteaga LA. Is COVID-19 a risk factor for severe preeclampsia? Hospital experience in a developing country. Eur J Obstet Gynecol Reprod Biol. 2021; 256: 502-503.
32. Sayad B, Rahimi Z. Blood coagulation parameters in patients with severe COVID-19 from Kermanshah province, islamic republic of Iran. East Mediterr Health J. 2020; 26(9): 999-1004.
33. Kayem G, Lecarpentier E, Deruelle P, Bretelle F, Azria E, Blanc J, et al. A snapshot of the Covid-19 pandemic among pregnant women in France. J Gynecol Obstet Hum Reprod. 2020; 49(7): 101826.
34. Sayad B, Karimi M, Rahimi Z. Sickle cell disease and COVID-19: Susceptibility and severity. Pediatr Blood Cancer. 2021; 68(8): e29075.
35. Abbas AM, Ahmed OA, Shaltout AS. COVID-19 and maternal preeclampsia: A synopsis. Scand J Immunol. 2020; 92(3): e12918.
36. Ahmed I, Eltaweel N, Antoun L, Rehal A. Severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP syndrome and acute kidney injury following SARS-CoV-2 infection. BMJ Case Rep. 2020; 13(8): e237521.
37. Choudhary A, Singh V, Bharadwaj M, Barik A. Pregnancy with SARS-CoV-2 infection complicated by preeclampsia and acute fatty liver of pregnancy. Cureus. 2021; 13(6): e15645.
38. Badr DA, Mattern J, Carlin A, Cordier AG, Maillart E, El Hachem L, et al. Are clinical outcomes worse for pregnant women at ≥20 weeks’ gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. Am J Obstet Gynecol. 2020; 223(5): 764-768.
39. Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, Seferovic MD, Aski SK, Arian SE, et al. Maternal death due to COVID-19. Am J Obstet Gynecol. 2020; 223(1): 109.e1-109.e16. 
40. Collin J, Byström E, Carnahan A, Ahrne M. Public health agency of sweden's brief report: pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in intensive care in Sweden. Acta Obstet Gynecol Scand. 2020; 99(7): 819-822.
41. Blitz MJ, Grünebaum A, Tekbali A, Bornstein E, Rochelson B, Nimaroff M, et al. Intensive care unit admissions for pregnant and nonpregnant women with coronavirus disease 2019. Am J Obstet Gynecol. 2020; 223(2): 290-291.
42. Qiancheng X, Jian S, Lingling P, Lei H, Xiaogan J, Weihua L, et al. Coronavirus disease 2019 in pregnancy. Int J Infect Dis. 2020; 95: 376-383. 
43. Diriba K, Awulachew E, Getu E. The effect of coronavirus infection (SARS-CoV-2, MERS-CoV, and SARS-CoV) during pregnancy and the possibility of vertical maternal-fetal transmission: a systematic 
review and meta-analysis. Eur J Med Res. 2020; 25(1): 39. 
44. Golden TN, Simmons RA. Maternal and neonatal response to COVID-19. Am J Physiol Endocrinol Metab. 2020; 319(2): E315-E319. 
45. Shanes ED, Mithal LB, Otero S, Azad HA, Miller ES, Goldstein JA. Placental pathology in COVID-19. Am J Clin Pathol. 2020; 154(1): 23-32. 
46. Hosier H, Farhadian SF, Morotti RA, Deshmukh U, Lu-Culligan A, Campbell KH, et al. SARS-CoV-2 infection of the placenta. J Clin Invest. 2020; 130(9): 4947-4953.
47. Gurunathan S, Kang MH, Kim JH. Diverse effects of exosomes on COVID-19: a perspective of progress from transmission to therapeutic developments. Front Immunol. 2021; 12: 716407. 
48. Mosquera-Heredia MI, Morales LC, Vidal OM, Barceló E, SilveraRedondo C, Vélez JI, et al. Exosomes: potential disease biomarkers and new therapeutic targets. Biomedicines. 2021; 9(8): 1061