胎儿免疫系统响应母体COVID-19的宫内激活

Q3 Medicine
N. R. Gashimova, L. Pankratyeva, V. Bitsadze, J. Khizroeva, N. Makatsariya, M. Tretyakova, A. Shkoda, K. Grigoreva, V. Tsibizova, J. Gris, F. Yakubova, D. Blinov, A. Makatsariya
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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. 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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). 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引用次数: 0

摘要

介绍。在怀孕期间,COVID-19对孕产妇健康和未出生婴儿的健康构成严重威胁。孕妇很可能因呼吸道病毒感染而出现并发症,随后因免疫和心肺系统的生理改变而出现危重情况。然而,孕妇无症状COVID-19可能伴有胎儿炎症反应综合征(FIRS),对新生儿的生命和健康造成不利的后遗症。目的:评估妊娠期母体COVID-19引起的胎儿炎症反应。材料和Мethods。对92名孕妇进行前瞻性随机比较研究。主组为62例妊娠COVID-19恢复期妇女:亚组1为30例产前4 ~ 6周PCR检测为SARS-CoV-2阳性的孕妇;亚组2 - 32例妊娠早期PCR检测到SARS-CoV-2的孕妇。对照组招募了30名健康孕妇。分析循环细胞因子-白细胞介素(IL) IL-1α、IL-6、IL-8、IL-10、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、肿瘤坏死因子α (TNF-α)、干扰素γ (IFN-γ)、巨噬细胞炎症蛋白-1β (mmp -1β)、C-X-C基序趋化因子配体10 (CXCL-10)和细胞标志物(CD86、CD80、CD4、CD25、CD25、CCR7)的水平。此外,所有新生儿都进行了胸腺超声筛查。亚组1与对照组相比,新生儿脐带血树突状细胞CD80和CD86表达显著上调(p = 0.023)。此外,与对照组相比,亚组1的脐带血样本中CD4+、CCR7+ T细胞的比例增加,而初始CD4+ T细胞的比例下降(p = 0.016)。结果发现,母亲的调节性CD4+CD25+Foxp3+ T细胞(Treg)计数无显著差异,而严重COVID-19(亚组2)母亲的Treg细胞功能活性明显受到抑制。亚组新生儿促炎因子和趋化因子水平显著高于对照组(p < 0.05)。而对照组和对照组产妇分娩后外周血细胞因子水平变化不显著。sars - cov -2阳性孕妇表现出强烈的抗原特异性T细胞反应。配对的COVID-19母亲所生的新生儿胸腺大小减小。胎儿炎症反应综合征发生在COVID-19时,其特征是胎儿免疫系统激活,促炎细胞因子的产生增加。孕妇的疾病严重程度与新生儿期FIRS强度无关,可从实验室参数的最小改变到器官和身体系统水平的发展后遗症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intrauterine activation of the fetal immune system in response to maternal COVID-19
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.
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