Barcelona Institute for Global Health, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
Barcelona Institute for Global Health, Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Front Immunol. 2022 Sep 27;13:999136. doi: 10.3389/fimmu.2022.999136. eCollection 2022.
SARS-CoV-2 infected pregnant women are at increased risk of severe COVID-19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth. However, little is known about the impact of SARS-CoV-2 infection on maternal and neonatal immunological profiles. In this study, we investigated the inflammatory and humoral responses to SARS-CoV-2 in maternal and cord blood paired samples. Thirty-six pregnant women were recruited at delivery at Hospital Sant Joan de Déu, Barcelona, Spain, between April-August 2020, before having COVID-19 available vaccines. Maternal and pregnancy variables, as well as perinatal outcomes, were recorded in questionnaires. Nasopharyngeal swabs and maternal and cord blood samples were collected for SARS-CoV-2 detection by rRT-PCR and serology, respectively. We measured IgM, IgG and IgA levels to 6 SARS-CoV-2 antigens (spike [S], S1, S2, receptor-binding domain [RBD], nucleocapsid [N] full-length and C-terminus), IgG to N from 4 human coronaviruses (OC43, HKU1, 229E and NL63), and the concentrations of 30 cytokines, chemokines and growth factors by Luminex. Mothers were classified as infected or non-infected based on the rRT-PCR and serology results. Sixty-four % of pregnant women were infected with SARS-CoV-2 (positive by rRT-PCR during the third trimester and/or serology just after delivery). None of the newborns tested positive for rRT-PCR. SARS-CoV-2 infected mothers had increased levels of virus-specific antibodies and several cytokines. Those with symptoms had higher cytokine levels. IFN-α was increased in cord blood from infected mothers, and in cord blood of symptomatic mothers, EGF, FGF, IL-17 and IL-15 were increased, whereas RANTES was decreased. Maternal IgG and cytokine levels showed positive correlations with their counterparts in cord blood. rRT-PCR positive mothers showed lower transfer of SARS-CoV-2-specific IgGs, with a stronger effect when infection was closer to delivery. SARS-CoV-2 infected mothers carrying a male fetus had higher antibody levels and higher EGF, IL-15 and IL-7 concentrations. Our results show that SARS-CoV-2 infection during the third trimester of pregnancy induces a robust antibody and cytokine response at delivery and causes a significant reduction of the SARS-CoV-2-specific IgGs transplacental transfer, with a stronger negative effect when the infection is closer to delivery.
SARS-CoV-2 感染的孕妇患 COVID-19 重症的风险高于未怀孕的女性，并且更有可能出现不良妊娠结局，如宫内/胎儿窘迫和早产。然而，对于 SARS-CoV-2 感染对母婴免疫谱的影响知之甚少。在这项研究中，我们研究了母亲和脐带血配对样本中 SARS-CoV-2 的炎症和体液反应。2020 年 4 月至 8 月，在西班牙巴塞罗那的桑乔德迪乌医院分娩时，招募了 36 名孕妇，当时还没有 COVID-19 可用疫苗。通过问卷调查记录了母亲和妊娠变量以及围产期结局。采集鼻咽拭子和母亲及脐带血样本，分别通过 rRT-PCR 和血清学检测 SARS-CoV-2。我们测量了 6 种 SARS-CoV-2 抗原（刺突[S]、S1、S2、受体结合域[RBD]、核衣壳[N]全长和 C 端）、4 种人类冠状病毒（OC43、HKU1、229E 和 NL63）的 IgG 至 N、以及通过 Luminex 测量 30 种细胞因子、趋化因子和生长因子的浓度。根据 rRT-PCR 和血清学结果，将母亲分为感染或未感染。64%的孕妇感染了 SARS-CoV-2（第三孕期 rRT-PCR 阳性，或分娩后即刻血清学阳性）。没有新生儿的 rRT-PCR 检测结果为阳性。感染 SARS-CoV-2 的母亲具有更高水平的病毒特异性抗体和几种细胞因子。有症状的母亲细胞因子水平更高。IFN-α在感染母亲的脐带血中增加，在有症状母亲的脐带血中，EGF、FGF、IL-17 和 IL-15 增加，而 RANTES 减少。母亲的 IgG 和细胞因子水平与脐带血中的对应物呈正相关。rRT-PCR 阳性的母亲表现出 SARS-CoV-2 特异性 IgG 的转移减少，当感染更接近分娩时，影响更强。携带男性胎儿的 SARS-CoV-2 感染母亲具有更高的抗体水平和更高的 EGF、IL-15 和 IL-7 浓度。我们的研究结果表明，妊娠晚期 SARS-CoV-2 感染会在分娩时诱导强烈的抗体和细胞因子反应，并导致 SARS-CoV-2 特异性 IgG 胎盘转移显著减少，当感染更接近分娩时，负面影响更强。
