Boelig Rupsa C, Chaudhury Sidhartha, Aghai Zubair H, Oliver Emily, Manusco Francesca, Berghella Vincenzo, Bergmann-Leitner Elke
medRxiv. 2021 Dec 7:2021.12.06.21267328. doi: 10.1101/2021.12.06.21267328.
To describe the profile and specificity of maternal and neonatal cord-blood antibody profile in response SARS-CoV-2 virus exposure.
This is a Prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020-February 2021. Primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in those patients with COVID-19 history. Serologic profile assessed with a multiplex platform. Antigens used were: HA-trimer Influenza A (Hong Kong H3), spike trimers for SARS-CoV-2, SARS-CoV-1, MERS-CoV, and betacoronaviruses HKU-1 and OC43, as well as the spike N-terminal domain (NTD), spike receptor binding domain (RBD), and nucleocapsid protein (N; full length) for SARS-CoV-2.
112 maternal samples and 101 maternal and cord blood pairs were analyzed. Thirty-seven had a known history of COVID-19 (positive PCR test) in the pregnancy and of those, 17 (47%) were diagnosed with COVID-19 within 30 days of delivery. Fifteen of remaining seventy-six (20%) without a known diagnosis had positive maternal serology. For those with history of COVID-19 we identified robust IgG response in maternal blood to CoV2 nucleocapsid (N), spike (S) full-length and S (RBD) antigens with more modest responses to the S (NTD) antigen. By contrast, the maternal blood IgM response appeared more specific to S (full-length), than N, S (RBD) or S (NTD) epitopes. There were significantly higher maternal and cord blood IgG response not just to CoV2 spike (p < 10 ), but also CoV1 spike (p < 10 ) and MERS spike (p < 10 ). By contrast, maternal IgM responses were more specific to CoV2 (p < 10 ), but to a lesser degree for CoV1 (p < 10 ), and no significant differences for MERS. Maternal and cord-blood IgG were highly correlated for both S and N (R = 0.96 and 0.94).
Placental transfer is efficient, with robust N and S responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. IgG antibodies are cross reactive with related CoV-1 and MERS spike epitopes while IgM, which cannot cross placenta to provide neonatal passive immunity, is more SARS CoV-2 specific. Neonatal cord blood may have significantly different fine-specificity than maternal blood, despite the high efficiency of IgG transfer.
描述孕产妇和新生儿脐带血抗体谱对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒暴露的反应特征和特异性。
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。主要目的是描述有新冠病毒疾病（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。用多重平台评估血清学特征。使用的抗原包括：甲型流感病毒（香港H3）血凝素三聚体、SARS-CoV-2、SARS-CoV-1、中东呼吸综合征冠状病毒（MERS-CoV）以及乙型冠状病毒HKU-1和OC43的刺突三聚体，还有SARS-CoV-2的刺突N端结构域（NTD）、刺突受体结合结构域（RBD）和核衣壳蛋白（N；全长）。
分析了112份孕产妇样本以及101对孕产妇和脐带血样本。37名孕妇在孕期有已知的COVID-19病史（PCR检测呈阳性），其中17名（47%）在分娩后30天内被诊断为COVID-19。其余76名无已知诊断的孕妇中有15名（20%）孕产妇血清学呈阳性。对于有COVID-19病史的患者，我们发现孕产妇血液中针对冠状病毒2核衣壳（N）、刺突（S）全长和S（RBD）抗原产生了强烈的IgG反应，而对S（NTD）抗原的反应较为适度。相比之下，孕产妇血液中的IgM反应似乎对S（全长）比对N、S（RBD）或S（NTD）表位更具特异性。孕产妇和脐带血中不仅对冠状病毒2刺突的IgG反应显著更高（p<10 ），对冠状病毒1刺突（p<10 ）和中东呼吸综合征刺突（p<10 ）的反应也显著更高。相比之下，孕产妇IgM反应对冠状病毒2更具特异性（p<10 ），但对冠状病毒1的特异性程度较低，对中东呼吸综合征则无显著差异。孕产妇和脐带血中的IgG在S和N方面高度相关（R = 0.96和0.94）。
胎盘转运效率高，对N和S有强烈反应。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。IgG抗体与相关的冠状病毒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IgM对SARS-CoV-2更具特异性。尽管IgG转运效率高，但新生儿脐带血的精细特异性可能与孕产妇血液有显著差异。
