Boelig Rupsa C, Chaudhury Sidhartha, Aghai Zubair H, Oliver Emily A, Mancuso Francesca, Berghella Vincenzo, Bergmann-Leitner Elke S
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (Drs Boelig, Oliver, and Berghella).
Department of Clinical Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA (Dr Boelig).
AJOG Glob Rep. 2022 Feb;2(1):100046. doi: 10.1016/j.xagr.2021.100046. Epub 2021 Dec 23.
Initial studies on COVID-19 in pregnancy have demonstrated a range of neutralizing activity, but little has been published on the full profile of SARS CoV-2 related antibodies in maternal and cordblood.
This study aimed to describe the profile and specificity of maternal and neonatal cord blood antibody profiles in response to SARS-CoV-2 virus exposure.
This was a prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020 to February 2021. The primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in patients with COVID-19 history. Serologic profile was assessed with a multiplex platform. Antigens used were hemagglutinin trimer influenza A (Hong Kong H3); spike trimers for SARS-CoV-2, SARS-CoV-1, Middle East respiratory syndrome coronavirus, and betacoronaviruses HKU-1 and OC43; and spike N-terminal domain, spike receptor-binding domain, and nucleocapsid protein (full length) for SARS-CoV-2.
Here, 112 maternal samples and 101 maternal and cord blood pairs were analyzed. Of note, 37 patients had a known history of COVID-19 (positive polymerase chain reaction test) during pregnancy. Of 36 patients, 16 (44%) were diagnosed with COVID-19 within 7 days of delivery. Moreover, 15 of the remaining 76 patients (20%) without a known diagnosis had positive maternal serology. For those with a history of COVID-19, we identified robust immunoglobulin G response in maternal blood to CoV-2 nucleocapsid, spike (full length), and spike (receptor-binding domain) antigens with more modest responses to the spike (N-terminal domain) antigen. In contrast, the maternal blood immunoglobulin M response seemed more specific to spike (full length) epitopes than nucleocapsid, spike (receptor-binding domain), or spike (N-terminal domain) epitopes. There were significantly higher maternal and cord blood immunoglobulin G responses not only to CoV-2 spike (127.1-fold; standard deviation, 2.0; <.00001) but also to CoV-1 spike (21.1-fold higher; standard deviation, 1.8; <.00001) and Middle East respiratory syndrome spike (6.9-fold higher; standard deviation, 2.5; <.00001). In contrast, maternal immunoglobulin M responses were more specific to CoV-2 spike (15.8-fold; standard deviation, 2.1; <.00001) but less specific to CoV-1 (2.5-fold higher; standard deviation, 0.71; <.00001) and no significant difference for Middle East respiratory syndrome. Maternal and cord blood immunoglobulin G antibodies were highly correlated for both spike and nucleocapsid (R=0.96 and 0.94, respectively).
Placental transfer was efficient, with robust nucleocapsid and spike responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. Immunoglobulin G antibodies were cross-reactive with related CoV-1 and Middle East respiratory syndrome spike epitopes, whereas immunoglobulin M antibodies, which cannot cross the placenta to provide neonatal passive immunity, were more SARS-CoV-2 specific. Neonatal cord blood may have significantly different fine specificity than maternal blood, despite the high efficiency of immunoglobulin G transfer.
关于妊娠期新型冠状病毒肺炎（COVID-19）的初步研究已证明了一系列中和活性，但关于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关抗体在母血和脐血中的完整情况，发表的内容很少。
本研究旨在描述孕产妇和新生儿脐血抗体谱对SARS-CoV-2病毒暴露的反应情况和特异性。
这是一项对2020年4月至2021年2月在托马斯·杰斐逊大学医院分娩患者的前瞻性队列研究。主要目的是描述有COVID-19病史患者独特的孕产妇和胎儿抗体表位滴度及特异性。采用多重平台评估血清学谱。使用的抗原包括甲型流感病毒血凝素三聚体（香港H3）；SARS-CoV-2、SARS-CoV-1、中东呼吸综合征冠状病毒以及β冠状病毒HKU-1和OC43的刺突三聚体；以及SARS-CoV-2的刺突N端结构域、刺突受体结合结构域和核衣壳蛋白（全长）。
本研究分析了112份孕产妇样本以及101对孕产妇和脐血样本。值得注意的是，37例患者在孕期有已知的COVID-19病史（聚合酶链反应检测呈阳性）。在36例患者中，16例（44%）在分娩后7天内被诊断为COVID-19。此外，其余76例无已知诊断的患者中有15例（20%）孕产妇血清学呈阳性。对于有COVID-19病史的患者，我们在母血中发现针对CoV-2核衣壳、刺突（全长）和刺突（受体结合结构域）抗原的强大免疫球蛋白G反应，而对刺突（N端结构域）抗原的反应较弱。相比之下，母血免疫球蛋白M反应似乎对刺突（全长）表位比对核衣壳、刺突（受体结合结构域）或刺突（N端结构域）表位更具特异性。孕产妇和脐血中免疫球蛋白G不仅对CoV-2刺突（高127.1倍；标准差为2.0；<.00001）而且对CoV-1刺突（高21.1倍；标准差为1.8；<.00001）和中东呼吸综合征刺突（高6.9倍；标准差为2.5；<.00001）的反应显著更高。相比之下，孕产妇免疫球蛋白M反应对CoV-2刺突更具特异性（高15.8倍；标准差为2.1；<.00001），但对CoV-1的特异性较低（高2.5倍；标准差为0.71；<.00001），对中东呼吸综合征无显著差异。孕产妇和脐血免疫球蛋白G抗体在刺突和核衣壳方面均高度相关（R分别为0.96和0.94）。
胎盘转运效率高，具有强大的核衣壳和刺突反应。为更好地理解COVID-19免疫，应同时研究核衣壳和刺突抗体反应。免疫球蛋白G抗体与相关的CoV-1和中东呼吸综合征刺突表位有交叉反应，而不能穿过胎盘提供新生儿被动免疫的免疫球蛋白M抗体对SARS-CoV-2更具特异性。尽管免疫球蛋白G转运效率高，但新生儿脐血的精细特异性可能与母血有显著差异。
