Gashimova Nilufar R, Pankratyeva Liudmila L, Bitsadze Victoria O, Khizroeva Jamilya Kh, Tretyakova Maria V, Grigoreva Kristina N, Tsibizova Valentina I, Gris Jean-Christophe, Degtyareva Natalia D, Yakubova Fidan E, Makatsariya Alexander D
Sechenov University, 2 bldg. 4, Bolshaya Pirogovskaya Str., 119991 Moscow, Russia.
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela Street, 117997 Moscow, Russia.
J Clin Med. 2023 Jun 25;12(13):4256. doi: 10.3390/jcm12134256.
: Contracting COVID-19 during pregnancy can harm both the mother and the unborn child. Pregnant women are highly likely to develop respiratory viral infection complications with critical conditions caused by physiological changes in the immune and cardiopulmonary systems. Asymptomatic COVID-19 in pregnant women may be accompanied by fetal inflammatory response syndrome, which has adverse consequences for the newborn's life and health. : To conduct an inflammatory response assessment of the fetus due to the effects of COVID-19 on the mother during pregnancy by determining pro-inflammatory cytokines, cell markers, T regulatory cells, T cell response, evaluation of cardiac function, and thymus size. : A prospective study included pregnant women ( = 92). The main group consisted of 62 pregnant women with COVID-19 infection: subgroup 1-SARS-CoV-2 PCR-positive pregnant women 4-6 weeks before delivery ( = 30); subgroup 2-SARS-CoV-2 PCR-positive earlier during pregnancy ( = 32). The control group consisted of 30 healthy pregnant women. In all pregnant women, the levels of circulating cytokines and chemokines (IL-1α, IL-6, IL-8, IL-10, GM-CSF, TNF-α, IFN-γ, MIP-1β, and CXCL-10) were determined in the peripheral blood and after delivery in the umbilical cord blood, and an analysis was performed of the cell markers on dendritic cells, quantitative and functional characteristics of T regulatory cells, and specific T cell responses. The levels of thyroxine and thyroid-stimulating hormone were determined in the newborns of the studied groups, and ultrasound examinations of the thymus and echocardiography of the heart were also performed. : The cord blood dendritic cells of newborns born to mothers who suffered from COVID-19 4-6 weeks before delivery (subgroup 1) showed a significant increase in CD80 and CD86 expression compared to the control group ( = 0.023). In the umbilical cord blood samples of children whose mothers tested positive for COVID-19 4-6 weeks before delivery (subgroup 1), the CD4+CCR7+ T cells increased with a concomitant decrease in the proportion of naive CD4+ T cells compared with the control group ( = 0.016). Significantly higher levels of pro-inflammatory cytokines and chemokines were detected in the newborns of subgroup 1 compared to the control group. In the newborns of subgroup 1, the functional activity of T regulatory cells was suppressed, compared with the newborns of the control group ( < 0.001). In all pregnant women with a severe coronavirus infection, a weak T cell response was detected in them as well as in their newborns. In newborns whose mothers suffered a coronavirus infection, a decrease in thymus size, transient hypothyroxinemia, and changes in functional parameters according to echocardiography were revealed compared with the newborns of the control group. : Fetal inflammatory response syndrome can occur in infants whose mothers suffered from a COVID-19 infection during pregnancy and is characterized by the activation of the fetal immune system and increased production of pro-inflammatory cytokines. The disease severity in a pregnant woman does not correlate with SIRS severity in the neonatal period. It can vary from minimal laboratory parameter changes to the development of complications in the organs and systems of the fetus and newborn.
孕期感染新冠病毒会对母亲和胎儿均造成伤害。孕妇极易因免疫和心肺系统的生理变化而出现严重的呼吸道病毒感染并发症。孕妇无症状新冠病毒感染可能伴有胎儿炎症反应综合征,这会对新生儿的生命和健康产生不良后果。
通过测定促炎细胞因子、细胞标志物、调节性T细胞、T细胞反应、评估心脏功能和胸腺大小,对孕期新冠病毒感染对母亲造成影响进而引发的胎儿炎症反应进行评估。
一项前瞻性研究纳入了孕妇(n = 92)。主要组由62例感染新冠病毒的孕妇组成:亚组1为分娩前4 - 6周SARS-CoV-2 PCR检测呈阳性的孕妇(n = 30);亚组2为孕期较早阶段SARS-CoV-2 PCR检测呈阳性的孕妇(n = 32)。对照组由30例健康孕妇组成。对所有孕妇外周血以及产后脐带血中循环细胞因子和趋化因子(IL-1α、IL-6、IL-8、IL-10、GM-CSF、TNF-α、IFN-γ、MIP-1β和CXCL-10)的水平进行了测定,并对树突状细胞上的细胞标志物、调节性T细胞的定量和功能特征以及特异性T细胞反应进行了分析。对研究组新生儿的甲状腺素和促甲状腺激素水平进行了测定,还对胸腺进行了超声检查以及对心脏进行了超声心动图检查。
分娩前4 - 6周感染新冠病毒的母亲所生新生儿的脐带血树突状细胞(亚组1)与对照组相比,CD80和CD86表达显著增加(P = 0.023)。分娩前4 - 6周新冠病毒检测呈阳性的母亲所生儿童的脐带血样本中,与对照组相比,CD4+CCR7+ T细胞增加,同时初始CD4+ T细胞比例下降(P = 0.016)。与对照组相比,亚组1新生儿中促炎细胞因子和趋化因子水平显著更高。与对照组新生儿相比,亚组1新生儿中调节性T细胞的功能活性受到抑制(P < 0.001)。在所有患有严重冠状病毒感染的孕妇及其新生儿中均检测到微弱的T细胞反应。与对照组新生儿相比,母亲感染冠状病毒的新生儿胸腺大小减小、出现短暂性甲状腺素减少症以及超声心动图显示功能参数发生变化。
胎儿炎症反应综合征可发生在孕期母亲感染新冠病毒的婴儿中,其特征为胎儿免疫系统激活和促炎细胞因子产生增加。孕妇疾病严重程度与新生儿期全身炎症反应综合征严重程度无关。其范围可从实验室参数的微小变化到胎儿和新生儿器官及系统并发症的发生。