COVID-19 can be severe in pregnant women, and have adverse consequences for the subsequent infant. We profiled the post-infectious immune responses in maternal and child blood as well as breast milk in terms of antibody and cytokine expression and performed histopathological studies on placentae obtained from mothers convalescent from antenatal COVID-19. Seventeen mother-child dyads (8 cases of antenatal COVID-19 and 9 healthy unrelated controls; 34 individuals in total) were recruited to the Gestational Immunity For Transfer (GIFT) study. Maternal and infant blood, and breast milk samples were collected over the first year of life. All samples were analyzed for IgG and IgA against whole SARS-CoV-2 spike protein, the spike receptor-binding domain (RBD), and previously reported immunodominant epitopes, as well as cytokine levels. The placentae were examined microscopically. The study is registered at clinicaltrials.gov under the identifier NCT04802278. We found high levels of virus-specific IgG in convalescent mothers and similarly elevated titers in newborn children. Thus, antenatal SARS-CoV-2 infection led to high plasma titers of virus-specific antibodies in infants postnatally. However, this waned within 3–6 months of life. Virus neutralization by plasma was not uniformly achieved, and the presence of antibodies targeting known immunodominant epitopes did not assure neutralization. Virus-specific IgA levels were variable among convalescent individuals’ sera and breast milk. Antibody transfer ratios and the decay of transplacentally transferred virus-specific antibodies in neonatal circulation resembled that for other pathogens. Convalescent mothers showed signs of chronic inflammation marked by persistently elevated IL17RA levels in their blood. Four placentae presented signs of acute inflammation, particularly in the subchorionic region, marked by neutrophil infiltration even though > 50 days had elapsed between virus clearance and delivery. Administration of a single dose of BNT162b2 mRNA vaccine to mothers convalescent from antenatal COVID-19 increased virus-specific IgG and IgA titers in breast milk, highlighting the importance of receiving the vaccine even after natural infection with the added benefit of enhanced passive immunity.

COVID-19 对孕妇来说可能很严重，并对随后的婴儿产生不良后果。我们从抗体和细胞因子表达方面分析了母婴血液以及母乳中的感染后免疫反应，并对从产前 COVID-19 恢复期的母亲获得的胎盘进行了组织病理学研究。妊娠免疫转移 (GIFT) 研究招募了 17 名母子二人组（8 例产前 COVID-19 病例和 9 例健康的无关对照；总共 34 人）。在出生第一年收集母亲和婴儿的血液和母乳样本。所有样本均针对整个 SARS-CoV-2 刺突蛋白、刺突受体结合域 (RBD) 和之前报道的免疫显性表位以及细胞因子水平进行了 IgG 和 IgA 分析。用显微镜检查胎盘。该研究注册于临床试验网标识符为 NCT04802278。我们发现恢复期母亲体内的病毒特异性 IgG 水平较高，新生儿体内的滴度也同样升高。因此，产前 SARS-CoV-2 感染导致婴儿出生后血浆中病毒特异性抗体滴度升高。然而，这种情况会在出生后 3-6 个月内减弱。血浆中和病毒的效果并不统一，针对已知免疫显性表位的抗体的存在也不能确保中和作用。恢复期个体的血清和母乳中病毒特异性 IgA 水平存在差异。抗体转移率和经胎盘转移的病毒特异性抗体在新生儿循环中的衰减与其他病原体相似。恢复期母亲表现出慢性炎症的迹象，其特征是血液中 IL17RA 水平持续升高。四个胎盘出现急性炎症迹象，特别是在绒毛膜下区域，以中性粒细胞浸润为特征，尽管病毒清除和分娩之间已经过去了 50 天以上。向产前 COVID-19 恢复期的母亲注射单剂 BNT162b2 mRNA 疫苗可增加母乳中病毒特异性 IgG 和 IgA 滴度，这凸显了即使在自然感染后接种疫苗的重要性，并具有增强被动免疫的额外好处。