W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Department of Gynecology and Obstetrics, Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Am J Obstet Gynecol. 2021 Sep;225(3):301.e1-301.e14. doi: 10.1016/j.ajog.2021.03.028. Epub 2021 Mar 30.
Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied.
This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women.
Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood.
Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy.
Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.
导致 2019 年冠状病毒病大流行的严重急性呼吸综合征冠状病毒 2 已在全球范围内导致发病率和死亡率。孕妇更容易感染严重的 2019 年冠状病毒病，并且早产的风险高于未感染的孕妇。尽管有此证据，但怀孕期间严重急性呼吸综合征冠状病毒 2 感染的免疫效应仍研究不足。
本研究旨在评估孕妇感染严重急性呼吸综合征冠状病毒 2 对母体和胎儿样本中炎症和体液反应的影响，并比较孕妇和非孕妇对严重急性呼吸综合征冠状病毒 2 的抗体反应。
使用在约翰霍普金斯医院检测到严重急性呼吸综合征冠状病毒 2 阳性（孕妇 22 例，非孕妇 17 例）或阴性（孕妇 11 例）的孕妇（n=33）和非孕妇（n=17）的样本分析对严重急性呼吸综合征冠状病毒 2 的免疫反应。我们测量了母体和脐带血样本中促炎和胎盘细胞因子信使 RNA、新生儿 Fc 受体表达和破伤风抗体转移。此外，我们评估了非孕妇、孕妇和脐血中收集的血清或血浆中的抗刺突免疫球蛋白 G、抗刺突受体结合域免疫球蛋白 G 和中和抗体对严重急性呼吸综合征冠状病毒 2 的反应。
实验室确诊的严重急性呼吸综合征冠状病毒 2 感染的孕妇在进行严重急性呼吸综合征冠状病毒 2 检测后 14 天内采集的血液样本中表达了更多的白细胞介素-1β，而不是白细胞介素 6。实验室确诊的严重急性呼吸综合征冠状病毒 2 感染的孕妇的抗刺突受体结合域免疫球蛋白 G 滴度也较低，并且与非孕妇相比，检测到中和抗体的可能性较小。尽管严重急性呼吸综合征冠状病毒 2 感染并未破坏胎盘内的新生儿 Fc 受体表达，但怀孕期间的感染抑制了母体对严重急性呼吸综合征冠状病毒 2 中和抗体的转移。
孕妇感染严重急性呼吸综合征冠状病毒 2 的特征是胎盘炎症和抗病毒抗体反应降低，这可能会影响怀孕期间对 2019 年冠状病毒病的治疗效果。此外，还需要更多地考虑胎盘炎症对新生儿健康的长期影响。
