Features of COVID-19 of Varying Severity in Pregnant Women

Aim. To determine the clinical andlaboratory features of COVID-19 of varying severity during pregnancy.

Design. Prospective cohort study.

Materials and methods. The study included 1476 pregnant women. The main group included 1,386 patients with COVID-19 at various stages of gestation, admitted to the maternity hospital of the Regional Clinical Hospital No. 2 in Chelyabinsk, repurposed into a COVID hospital to provide medical care to pregnant women, women inlabor and postpartum women with COVID-19 , as well as their newborns, in the territory of Chelyabinsk and the Chelyabinsk region, during the 1^st-4^th waves of the COVID-19 pandemic. Depending on the severity of COVID-19, patients of the main group were divided into 4 subgroups: Subgroup 1 — pregnant women with mild COVID-19 (n = 482), Subgroup 2 — women with moderate COVID-19 (n = 718), Subgroup 3 — patients with severe COVID-19 (n = 147), Subgroup 4 — pregnant women with extremely severe COVID-19 (n = 21). The comparison group consisted of 90 women admitted to the maternity hospital of the Regional Clinical Hospital No. 3 in Chelyabinsk from July 2020 to February 2021 in the third trimester of gestation. The comparison group consisted of 90 pregnant women admitted to the maternity hospital of the Regional Clinical Hospital No. 3 in Chelyabinsk from July 2020 to February 2021 in the third trimester of gestation.

Results. The leading symptoms of infection in pregnant women with COVID-19 were fever, general weakness, dry cough with difficult-toseparate phlegm, and shortness of breath. Statistically significantly more often in severe and extremely severe COVID-19 at the time of¹⁵ hospitalization, chest congestion and pain, and rapid heartbeat were noted. Against the background of severe and extremely severe infection, and in comparison with the group of patients without COVID-19,lymphocytopenia, hypoproteinemia, highlevels of band neutrophils, alanine aminotransferase, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), C-reactive protein, ferritin, procalcitonin, soluble fibrin monomer complexes, and D-dimer were statistically significantly more often recorded.

Conclusion. Clinical signs of severe and extremely severe COVID-19 in pregnant women include general weakness, dry cough with difficult-toseparate phlegm, shortness of breath, chest congestion and pain, and rapid heartbeat. Laboratory factors statistically significantly associated with the progression of COVID-19 to extremely severe cases during pregnancy are the highestlevels of AST, LDH, and hypoproteinemia with thelowestlevel of total protein in the blood serum determined at the time of hospitalization. The information obtained will help optimize the prediction of the most unfavorable form of COVID-19 for pregnant women — extremely severe infection.

1. Belokrinitskaya T.E., Artymuk N.V., Filippov O.S., Frolova N.I. Clinical course, maternal and perinatal outcomes of 2019 novel coronavirus infectious disease (COVID-19) in pregnant women in Siberia and Far East. Obstetrics and Gynecology. 2021;2:48–54. (in Russian). DOI: 10.18565/aig.2021.2.48-54

2. Narang K., Enninga E.A., Gunaratne M.D., Ibirogba E.R. et al. SARSCoV-2 infection and COVID-19 during pregnancy: a multidisciplinary review. Mayo Clin. Proc. 2020;95(8):1750–65. DOI: 10.1016/j.mayocp.2020.05.011

3. Villar J., Ariff S., Gunier R.B., Thiruvengadam R. et al. Maternal and neonatal morbidity and mortality among pregnant women with and without COVID-19 infection: the INTERCOVID Multinational Cohort Study. JAMA Pediatr. 2021;175(8):817–26. DOI: 10.1001/jamapediatrics.2021.1050

4. Allotey J., Stallings E., Bonet M., Yap M. 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. DOI: 10.1136/bmj.m3320

5. Jafari M., Pormohammad A., Sheikh Neshin S.A., Ghorbani S. et al. Clinical characteristics andoutcomes of pregnant women with COVID19 and comparison with control patients: a systematic review and meta-analysis. Rev. Med. Virol. 2021;31(5):1–16. DOI: 10.1002/rmv.2208

6. Voropaeva E.E., Khaidukova Yu.V., Kazachkova E.A., Kazachkov E.L. et al. Clinical and laboratory features and maternal outcomes in pregnant women with critical lung damage in the COVID-19. Ural Medical Journal. 2024;23(1):90–103. (in Russian). DOI: 10.52420/2071-5943-2024-23-1-90-103

7. Smith E.R., Oakley E., Grandner G.W., Ferguson K. et al. Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis. BMJ Glob. Health. 2023;8(1):e009495. DOI: 10.1136/bmjgh-2022-009495

8. Elshafeey F., Magdi R., Hindi N., Elshebiny M. et al. Systematic scoping review of COVID-19 during pregnancy and childbirth. Int. J. Gynaecol. Obstet. 2020;150(1):47–52. DOI:10.1002/ijgo.13182

9. Shree P., Mittal N., Vishwakarma S., Verma V. et al. Maternal and perinatal outcomes of COVID-19-positive pregnant women. Cureus. 2022;14(6):e26411. DOI: 10.7759/cureus.26411

10. Gareyeva A.I., Mozgovaya E.V., Belopolskaya M.A., Kovalchuk A.S. et al. Experience in managing severe and extremely severe COVID-19 in pregnant women. Journal of Obstetrics and Women's Diseases. 2022;71(1):11–22. (in Russian). DOI: 10.17816/JOWD72169

11. Ishchenko L.S., Voropaeva E.E., Khaidukova Y.V., Kazachkova E.A. et al. Peculiarities of hemostasis in pregnant women during manifestation of new coronavirus infection COVID-19 in the third trimester of gestation. South Ural Medical Journal. 2021;3:60–74. (in Russian)

12. Ishchenko L.S., Voropaeva E.E., Kazachkova E.A., Kazachkov E.L. et al. Erythropoietin as a predictor of the extremely severe course of the new coronavirus infection COVID-19 in pregnant women. Yakut Medical Journal. 2024;2:59–63. (in Russian). DOI: 10.25789/YMJ.2024.86.14

13. Zhang B., Zhou X., Zhu C., Song Y. et al. Immune phenotyping based on the neutrophil-to-lymphocyte ratio and IgG level predicts disease severity and outcome for patients with COVID-19. Front. Mol. Biosci. 2020;7:157. DOI: 10.3389/fmolb.2020.00157

14. Chen N., Zhou M., Dong X., Qu J. et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. DOI: 10.1016/S0140-6736(20)30211-7

15. Huang C., Wang Y., Li X., Ren L. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. DOI: 10.1016/S0140-6736(20)30183-5

16. Zhang C., Shi L., Wang F.S. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol. Hepatol. 2020;5(5):428–30. DOI: 10.1016/S2468-1253(20)30057-1

17. Xie H., Zhao J., Lian N., Lin S. et al. Clinical characteristics of non-ICU hospitalized patients with coronavirus disease 2019 and liver injury: a retrospective study. Liver Int. 2020;40(6):1321–6. DOI: 10.1111/liv.14449

18. Liu D., Li L., Wu X., Zheng D. et al. Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR Am. J. Roentgenol. 2020;215(1):127–32. DOI: 10.2214/AJR.20.23072

19. Turan O., Hakim A., Dashraath P., Jeslyn W.J.L. et al. Clinical characteristics, prognostic factors, and maternal and neonatal outcomes of SARS-CoV-2 infection among hospitalized pregnant women: a systematic review. Int. J. Gynecol. Obstet. 2020;151(1):7–16. DOI: 10.1002/ijgo.13329ijgo.13329

20. Zhong Y., Cao Y., Zhong X., Peng Z. et al. Immunity and coagulation and fibrinolytic processes may reduce the risk of severe illness in pregnant women with coronavirus disease 2019. Am. J. Obstet. Gynecol. 2021;224(4):393.e1–25. DOI: 10.1016/j.ajog.2020.10.032

21. Klok F.A., Kruip M.J.H.A., van der Meer N.J.M., Arbous M.S. et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020;191:145–7. DOI: 10.1016/j.thromres.2020.04.013

22. Thachil J., Tang N., Gando S., Falanga A. et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J. Thromb. Haemost. 2020;18(5):1023–6. DOI: 10.1111/jth.14810

23. Koumoutsea V.E., Vivanti A.J., Shehata N., Benachi A. et al. COVID19 and acute coagulopathy in pregnancy. J. Thromb. Haemost. 2020;18(7):1648–52. DOI: 10.1111/jth.14856

24. Gungor B., Atici A., Baycan O.F., Alici G. et al. Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: a systematic review and meta-analysis. Am. J. Emerg. Med. 2021;39:173–9. DOI: 10.1016/j.ajem.2020.09.018