COVID-19: gender characteristics of the course, perinatal risks and possible ways to prevent complications
Keywords:COVID-19, pregnancy, complications, miscarriage, nutritional deficiencies, correction, prevention
The article contains modern data of the characteristics, course and impact on pregnant women, postpartum women, fetus and newborn of the SARS-CoV-2. The opinions of experts from different countries of the world on the consequences of coronavirus disease depending on racial, ethnic, age differences and delivery time. Immunological and hormonal protection during pregnancy against viral influences is noted.
In the context of a pandemic, the number of premature births (for various reasons) and the birth of children with low birth weight significantly increased, but their relationship with COVID-19 infection has not been proven. Risk factors for the hospitalization of pregnant woman infected with COVID-19 are high body mass index, obesity and concomitant diseases (diabetes mellitus, hypertension. Women in older reproductive age also need hospitalization more often. During pregnancy, innate and adaptive immune responses shift from an inflammatory to an anti-inflammatory phenotype to prevent affection of the fetus and promote passive transmission of maternal antibodies to the fetus. These COVID-19 protection effects are largely mediated by estradiol and progesterone.
New data on the impact of COVID-19 on erythropoiesis, hemoglobin and ferritin levels are presented, and risk groups of a more severe course of the disease are identified: elderly adults, patients, patients with arterial hypertension, obesity and diabetes mellitus, pregnant women, patients with primary and acquired immunodeficiency, with oppression of the hematopoiesis, HIV-infected and with cancer. The algorithm of outpatient monitoring of pregnant women during a pandemic (self-assessment of the state, online control, etc.) is given.
Some current world protocols for the COVID-19 prevention and treatment have been analyzed and a modification adapted for Ukrainian pregnant women has been proposed. A method is proposed for the prevention miscarriage and nutritional deficits – one of the frequent and dangerous COVID-19 complications in pregnant women.
Bril, Y.A. “Preventive and treatment strategies for iron deficiency in the practice of obstetrician-gynecologist.” StatusPraesens. Gynecology, obstetrics, infertile marriage 39.3 (2017): 79–88.
Zhabchenko, I.A. “A few steps to…, or how to protect a pregnant woman from iron deficiency and anemia.” Reproductive endocrinology 4.54 (2020): 2–9.
Zhabchenko, I.A. “Modern view on the role of folate in the prevention of perinatal problems.” Reproductive endocrinology 2.46 (2019): 57–61.
Zaichenko, A.V. “Folates and omega-3-PUFA in obstetrics: more than prevention of neural tube defects.” Health of Ukraine. Gynecology. Obstetrics. Reproductology 1(2018): 1–4.
Medved, V.I., Kirilchuk, M.E. “Prevention of iron deficiency and anemia in pregnant women.” Female doctor 4.84 (2019): 28–30.
Ministry of Health of Republic of Kazakhstan. Clinical protocol of diagnosis and treatment. Coronavirus infection COVID-19 in pregnant women and in the postpartum period. Nur-Sultan (2020): 60 p.
Ministry of Health of Russian Federation. Organization of medical care for pregnant women, parturients, parturients and newborns with a new coronavirus infection COVID-19. Methodical recommendations. Version 3 (25.01.2021). Moscow. Ministr y of Health of the Russian Federation (2021): 119 p.
Ministry of Health of Ukraine Protocol of provision of medical care for the treatment of coronavirus disease (COVID-19). Order of the MoH of Ukraine dated 02.04.2020 № 762 (as amended by MoH of Ukraine dated 06.04.2021 № 638).
Radzinskiy, V.E. “On definiteness and uncertainty in obstetrics in coronavirus pandemic.” StatusPraesens 3.68 (2020): 22–3.
Solovieva, A.V, Sturov, V.G., et al. Anemia and reproductive health.Moscow. Editorial Board of StatusPraesens Journal (2019): 200 p.
Stuklov, N.I. “Ferrodeficiency syndromes in questions and answers.” StatusPraesens 5.42 (2017): 120–4.
Stuklov, N.I., Knyazev, O.V., Parfenov, A.I., et al. “Comparative efficacy of a new sucrosomal form of iron for oral administration and intravenous ferrotherapy in the treatment of anemia in patients with inflammatory bowel disease.” Clinical medicine 95.12 (2017): 1112–7.
Fedorova, T.A., Borzykina, O.M., Bakuridze, E.M. “Correction of iron deficiency anemia in patients with gynecological diseases using liposomal iron.” Gynecology 1.19 (2017): 68–72.
Shikh, E.V., Bril, Y.A. “Iron deficiency: a catastrophe for neurogenesis.” StatusPraesens 10 (2018): 82–8.
Alghamdi, I.G., Hussain, I.I., Almalki, S.S., El-Sheemy, M.A. “The pattern of middle east respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health.” Int J Gen Med 7 (2014): 417–23.
Amadori, A., Zamarchi, R., De Silvestro, G., et al. “Genetic control of the CD4/CD8 T-cell ratio in humans. ” Nat Med 1.12 (1995): 1279–83. DOI: 10.1038/nm1295-1279
Butterworth, M., McClellan, B., Allansmith, M. “Influence of sex in immunoglobulin levels.” Nature 214.5094 (1967): 1224–5.
Carrel, L., Brown, C.J. “When the Lyon (ized chromosome) roars: ongoing expression from an inactive X chromosome.” Philos Trans R Soc Lond B Biol Sci 372.1733 (2017): 20160355.
Centers for Disease Control and Prevention (CDC). Current information about COVID-19. Available from: [https://www.cdc.gov/coronavirus/2019-nCoV/index.html].
Chen, G., Wu, D., Guo, W., et al. “Clinical and immunological features of severe and moderate coronavirus disease.” J Clin Invest 130.5 (2020): 2620–9.
Chen, L., Li, Q., Zheng, D., et al. “Clinical characteristics of pregnant women with Covid-19 in Wuhan, China.” N Engl J Med 382.25 (2020): e100.
Cheng, L., Li, H., Li, L., et al. “Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis.” J Clin Lab Anal 34.10 (2020): e23618. DOI: 10.1002/jcla.23618
Chousterman, B.G., Swirski, F.K., Weber, G.F. “Cytokine storm and sepsis disease pathogenesis.” Semin Immunopathol 39.5 (2017): 517–28.
Docherty, A.B., Harrison, E.M., Green, C.A., et al. “Features of 16 749 hospitalised UK patients with COVID-19 using the ISARIC WHO clinical characterisation protocol.” medRxiv (2020). DOI: 10.1101/2020.04.23.20076042
Doria, A., Iaccarino, L., Arienti, S., et al. “Th2 immune deviation induced by pregnancy: the two faces of autoimmune rheumatic diseases.” Reprod Toxicol 22.2 (2006): 234–41.
Grasselli, G., Zangrillo, A., Zanella, A., et al. “Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy.” JAMA 323.16 (2020): 1574–81.
Guan, W.J., Ni, Z.Y., Hu, Y., et al. “Clinical characteristics of coronavirus disease 2019 in China. ” N Engl J Med 382 (2020):1708–20.
Hantoushzadeh, S., Shamshirsaz, A.A., Aleyasin, A., et al. “Maternal death due to COVID-19 disease.” Am J Obstet Gynecol 223.1 (2020): 109.e1–109.e16.
Klein, S.L., Jedlicka, A., Pekosz, A. “The Xs and Y of immune responses to viral vaccines.” Lancet Infect Dis 10.5 (2010): 338–49.
Klein, S.L., Flanagan, K.L. “Sex differences in immune responses.” Nat Rev Immunol 16.10 (2016): 626–38.
Marina, S., Piemonti, L. “Gender and age effects on the rates of infection and deaths in individuals with confirmed SARS-CoV-2 infection in six European countries.” SSRN online (2020). DOI: 10.2139/ssrn.3576790
Marik, P. “COVID-19 management protocol.” Available from: [https://www.evms.edu/media/evms_public/departments/internal_medicine/Marik_Critical_Care_COVID-19_Protocol. pdf], last accessed June 03, 2021.
McGonagle D., Sharif, K., O’Regan, A., Bridgewood, C. “The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease.” Autoimmun Rev 19.6 (2020): 102537.
Mehta, P., McAuley, D.F., Brown, M., et al. “COVID-19: consider cytokine storm syndromes and immunosuppression.” Lancet 395.10229 (2020): 1033–4.
Migeon, B.R. Females are Mosaics: X Inactivation and Sex Differences in Disease. 2nd ed. New York. Oxford University Press (2013).
Moussa, H.M., et al. “Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks.” Future Sci OA 2.2 (2016). DOI: 10.4155/fsoa-2015-0015
Move-Jarvis, F., Klein, S.L., Levin, E.R. “Estradiol, progesterone, immunomodulation and outcomes COVID-19.” Endocrinology 161.9 (2020).
Pazos, M., Sperling, R.S., Moran, T.M., Kraus, T.A. “The influence of pregnancy on systemic immunity.” Immunol Res 54.1–3 (2012): 254–61.
Phiel, K.L., Henderson, R.A., Adelman, S.J., Elloso, M.M. “Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations.” Immunol Lett 97.1 (2005): 107–13.
Centers for Disease Control and Prevention (CDC). Pregnant and Recently Pregnant People. At increased risk for severe illness from COVID-19. Available from: [https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/pregnant-people.html], last acsessed May 13, 2021.
Qiancheng, X., Jian, S., Lingling, P., et al. “Coronavirus disease 2019 in pregnancy.” Int J Infect Dis 95 (2020): 376–83.
Richardson, S., Hirsch, J.S., Narasimhan, M., et al. “COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area. ” JAMA 323.20 (2020): 2052–9.
Robinson, D.P., Klein, S.L. “Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis.” Horm Behav 62.3 (2012): 263–71.
Royal College of Obstetricians and Gynecologists. Coronavirus (COVID-19) Infection in Pregnancy, Information for healthcare professionals, Vers. 12 (2020). Available from: [https://www.rcog.org.uk/en/guidelines-research-services/guidelines/coronavirus-pregnancy], last accessed June 03, 2021.
Scully, E., Haverfield, J., Ursin, R., et al. “Sex is a variable in immune responses and COVID-19 outcomes.” Nat Rev Immunol 20 (2020): 442–7.
Straub, R.H. “The complex role of estrogens in inflammation.” Endocr Rev 28.5 (2007): 521–74.
Szekeres-Bartho, J., Faust, Z., Varga, P., et al. “The immunological pregnancy protective effect of progesterone is manifested via controlling cytokine production.” Am J Reprod Immunol 35.4 (1996): 348–51.
Tanaka, T., Narazaki, M., Kishimoto, T. “Immunotherapeutic implications of IL-6 blockade for cytokine storm.” Immunotherapy 8.8 (2016): 959–70.
Tukiainen, T., Villani, A.C., Yen, A., et al. “Landscape of X chromosome inactivation across human tissues.” Nature 550.7675 (2017): 244–8.
WHO and the International Bank for Reconstruction and Development. Tracking Universal Health Coverage: 2017 Global Monitoring Report (2017): 88 p.
World Health Organization. Daily iron supplementation in adult women and adolescent girls: Guideline. Geneva. WHO (2016).
World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva. WHO (2017).
Ye, Q., Wang, B., Mao, J. “The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19.” J Infect 80.6 (2020): 607–13.
Yeoh, Y.K., Zuo, T., Lui, G.C., et al. “Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.” BMJ 70.4 (2021): 698–706.
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