To evaluate the development of neutralizing Anti-Spike Protein IgG (Anti-S-IgG) during twin pregnancies before conception vs. during pregnancy. In this prospective study, three blood samples were collected from pregnant women and subjected to anti-S-IgG immunodiagnostics. The patient’s medical records, including vaccination and PCR test results, were collected from the hospital’s electronic database. Age-matched non-pregnant women were used as a control group. We enrolled 83 women with twin pregnancies. 49 women were vaccinated before conception, 21 women were vaccinated during pregnancy, and 13 were not vaccinated. Of the 13 women who weren’t vaccinated, three became positive during pregnancy, and all three were severely ill. By contrast, in women who were vaccinated during or before pregnancy, COVID-19 infection during pregnancy caused only mild symptoms. A ten-fold lower level of neutralizing Anti-S-IgG in the 3rd trimester was observed in healthy women who were vaccinated before conception and remained healthy until discharge from the hospital after delivery 1605 (IQR: 763–2410) compared to the healthy women who were vaccinated during pregnancy 152 AU/mL (IQR: 54–360). This difference was higher among women who were infected by COVID-19 (as verified by a positive PCR test). The third-trimester level of neutralizing Ant-S-IgG in the infected group was 4770 AU/mL (4760–6100) in infected women vaccinated before conception compared to those vaccinated during pregnancy who had 70 AU/mL (IQR: 20–170) (p < 0.001). In women vaccinated at 13–16 weeks gestation, neutralizing Anti-S-IgG at 20–22 weeks went up to 372 AU/mL (IQR: 120–1598) but rapidly dropped to 112 AU/mL (IQR: 54–357) at 28–30 weeks, (p < 0.001), a faster decline than in women vaccinated at a median 22 weeks before conception. Being infected by COVID-19 before conception was linked to having low Anti-S-IgG levels during pregnancy, whereas being infected by COVID-19 during pregnancy led to a very high response in the 3rd trimester. In twin pregnancies, significantly lower neutralizing Anti-S-IgG levels were observed in women vaccinated during pregnancy compared to those vaccinated before conception, whether infected or not infected by COVID-19. A full course of vaccination before conception is recommended.

Trial registration. ClinicalTrials.gov Protocol Registration and Results System (PRS) Receipt Release Date: October 4, 2021. https://clinicaltrials.gov/ ID: NCT04595214.

旨在评估受孕前与怀孕期间双胎妊娠期间中和抗尖峰蛋白 IgG (Anti-S-IgG) 的发展情况。在这项前瞻性研究中，从孕妇身上采集了三份血液样本，并进行了抗 S-IgG 免疫诊断。患者的医疗记录，包括疫苗接种和 PCR 检测结果，均从医院的电子数据库中收集。年龄匹配的未怀孕妇女被用作对照组。我们招募了 83 名怀有双胞胎的女性。 49名女性在受孕前接种了疫苗，21名女性在怀孕期间接种了疫苗，13名女性未接种疫苗。在 13 名未接种疫苗的女性中，有 3 名在怀孕期间呈阳性，而且三人均病情严重。相比之下，在怀孕期间或怀孕前接种疫苗的女性中，怀孕期间感染 COVID-19 仅引起轻微症状。与健康女性相比，在受孕前接种疫苗并在产后出院前保持健康的健康女性中，在妊娠第三个月观察到的中和性抗 S-IgG 水平低十倍 1605 (IQR: 763–2410)怀孕期间接种疫苗的人为 152 AU/mL (IQR: 54–360)。这种差异在感染了 COVID-19 的女性中更高（经阳性 PCR 检测证实）。在受孕前接种疫苗的受感染妇女中，受感染组的妊娠晚期中和性 Ant-S-IgG 水平为 4770 AU/mL (4760–6100)，而在怀孕期间接种疫苗的受感染妇女的中和 Ant-S-IgG 水平为 70 AU/mL（IQR：20–170） ）（p  < 0.001）。在妊娠 13-16 周接种疫苗的女性中，中和抗 S-IgG 在 20-22 周时上升至 372 AU/mL (IQR: 120-1598)，但迅速下降至 112 AU/mL (IQR: 54-357)在 28-30 周（p  < 0.001），比受孕前平均 22 周接种疫苗的女性下降得更快。受孕前感染 COVID-19 与怀孕期间抗 S-IgG 水平较低有关，而怀孕期间感染 COVID-19 会导致妊娠第三个月的反应非常高。在双胎妊娠中，与受孕前接种疫苗的女性相比，无论是否感染 COVID-19，在怀孕期间接种疫苗的女性中和性抗 S-IgG 水平显着降低。建议在受孕前进行全程疫苗接种。

试用注册。 ClinicalTrials.gov 方案注册和结果系统 (PRS) 收据发布日期：2021 年 10 月 4 日。https://clinicaltrials.gov/ ID：NCT04595214。