Intrauterine activation of the fetal immune system in response to maternal COVID-19
https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.404
Abstract
Introduction. During pregnancy COVID-19 poses a serious threat to both maternal health and health of paired unborn child. Pregnant women have a high probability of complications due to respiratory viral infections followed by developing critical conditions caused by physiologically altered immune and cardiopulmonary systems. However, asymptomatic COVID-19 in pregnant women may be accompanied by fetal inflammatory response syndrome (FIRS) that results in unfavorable sequelae for neonatal life and health.
Aim: to assess a fetal inflammatory response resulting from maternal COVID-19 in pregnancy.
Materials and Мethods. A prospective randomized comparative study involving 92 pregnant women was carried out. The main group included 62 pregnant COVID-19 convalescent women: subgroup 1 consisted of 30 pregnant women found to be positive for SARS-CoV-2 by using polymerase chain reaction (PCR) 4–6 weeks before delivery; subgroup 2 – 32 pregnant women with SARS-CoV-2 detected by PCR earlier during pregnancy. The control group enrolled 30 healthy pregnant women. The level of circulating cytokines – interleukins (IL) IL-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), macrophage inflammatory protein-1β (MIP-1β), C-X-C motif chemokine ligand 10 (CXCL-10) and cell markers (CD86, CD80, CD4, CD25, CD25, CCR7) were analyzed. In addition, all neonates underwent thymus gland ultrasound screening.
Results. Cord blood dendritic cells from neonates born to mothers in subgroup 1 vs. control group showed a significantly upregulated expression of CD80 and CD86 (p = 0.023). Moreover, such cord blood samples in subgroup 1 were found to have increased percentage of CD4+, CCR7+ T cells paralleled with decreased proportion of naive CD4+ T cells as compared with control group (p = 0.016). It was found that count of maternal regulatory CD4+CD25+Foxp3+ T cells (Treg) did not differ significantly, whereas Treg cell functional activity in mothers with severe COVID-19 (subgroup 2) was significantly suppressed. Significantly higher level of neonatal proinflammatory cytokines and chemokines was detected in subgroup 1 vs. control group (p < 0.05). However, the cytokines level in maternal peripheral blood samples in main and control groups upon delivery was changed insignificantly. SARS-CoV-2-positive pregnant women showed a strong antigen-specific T cell response. A reduced thymus size was found in neonates born to paired COVID-19 mothers.
Conclusion. Fetal inflammatory response syndrome occurs upon COVID-19, which is characterized by activated fetal immune system and increased production of pro-inflammatory cytokines. The disease severity in pregnant women has no correlation with FIRS intensity during neonatal period and can vary from minimally altered laboratory parameters to developing sequelae at organ and body system levels.
About the Authors
N. R. GashimovaRussian Federation
Nilufar R. Gashimova – MD, Postgraduate Student, Department of Obstetrics, Gynecology and Perinatal Medicine
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
L. L. Pankratyeva
Russian Federation
Liudmila L. Pankratyeva – MD, Dr Sci Med, Associate Professor, Professor, Department of Pediatrics and Health Organization, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology; Neonatologist, Hematologist, Head of the Clinical Research Center, Vorokhobov City Clinical Hospital No 67
1 Samora Machel Str., Moscow 117997
2/44 Salyama Adilya Str., Moscow 123423
V. O. Bitsadze
Russian Federation
Victoria O. Bitsadze – MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health
Scopus Author ID: 6506003478, Researcher ID: F-8409-2017
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
J. Kh. Khizroeva
Russian Federation
Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine
Scopus Author ID: 57194547147, Researcher ID: F-8384-2017
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
N. A. Makatsariya
Russian Federation
Nataliya A. Makatsariya – MD, PhD, Associate Professor, Department of Obstetrics, Gynecology and Perinatal Medicine
Researcher ID: F-8406-2017
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
M. V. Tretyakova
Russian Federation
Maria V. Tretyakova – MD, PhD, Obstetrician-Gynecologist, Assistant, Department of Obstetrics, Gynecology and Perinatal Medicine
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
A. S. Shkoda
Russian Federation
Andrey S. Shkoda – MD, Dr Sci Med, Professor, Chief Physician
2/44 Salyama Adilya Str., Moscow 123423
K. N. Grigoreva
Russian Federation
Kristina N. Grigoreva – MD, Assistant, Department of Obstetrics, Gynecology and Perinatal Medicine
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
V. I. Tsibizova
Russian Federation
Valentina I. Tsibizova – MD, PhD, Obstetrician-Gynecologist, Research Laboratory of Operative Gynecology, Institute of Perinatology and Pediatrics; Physician, Department of Functional and Ultrasound Diagnostics
2 Akkuratova Str., Saint Petersburg 197341
J.-C. Gris
Russian Federation
Jean-Christophe Gris – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health, Sechenov University; Professor of Haematology, Head of the Laboratory of Haematology, Faculty of Biological and Pharmaceutical Sciences, Montpellier University and University Hospital of Nîmes, France; Foreign Member of RAS
Scopus Author ID: 7005114260, Researcher ID: AAA-2923-2019
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
163 Rue Auguste Broussonnet, Montpellier 34090, France
F. E. Yakubova
Russian Federation
Fidan E. Yakubova – MD, Clinical Resident, Department of Obstetrics and Gynecology
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
D. V. Blinov
Russian Federation
Dmitry V. Blinov – MD, PhD, MBA, Assistant, Department of Sports Medicine and Medical Rehabilitation, Sklifosovsky Institute of Clinical Medicine, Sechenov University; Head of Medical and Scientific Affairs, Institute for Preventive and Social Medicine; Associate Professor, Department of Sports, Physical and Rehabilitation Medicine, Moscow Haass Medical – Social Institute
Scopus Author ID: 6701744871, Researcher ID: E-8906-2017, RSCI: 9779-8290
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
4–10 Sadovaya-Triumfalnaya Str., Moscow 127006
5 bldg. 1–1a, 2-ya Brestskaya Str., Moscow 123056
A. D. Makatsariya
Russian Federation
Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health, Sechenov University; Vice-President of the Russian Society of Obstetrican-Gynecologists (RSOG); Honorary Doctor of the Russian Federation; Emeritus Professor of the University of Vienna
2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991
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Review
For citations:
Gashimova N.R., Pankratyeva L.L., Bitsadze V.O., Khizroeva J.Kh., Makatsariya N.A., Tretyakova M.V., Shkoda A.S., Grigoreva K.N., Tsibizova V.I., Gris J., Yakubova F.E., Blinov D.V., Makatsariya A.D. Intrauterine activation of the fetal immune system in response to maternal COVID-19. Obstetrics, Gynecology and Reproduction. 2023;17(2):188-201. (In Russ.) https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.404

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