Coronavirus disease 2019 (COVID-19) infection in pregnancy has been associated with preterm delivery and preeclampsia. A less frequent and underrecognized complication is extensive placental infection which is associated with high rates of perinatal morbidity and mortality. The frequency, early pathogenesis, and range of lesions associated with this infection are poorly understood. We conducted a population-based study of placental pathology from all mothers with COVID-19 (n=271) over an 18-month period delivering within our health system. The overall prevalence of diffuse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) placentitis, as defined by typical histology and immunohistochemical (IHC) staining for SARS-CoV-2 spike protein, was 14.8/1000, but increased to 59/1000 in preterm births. We also identified 3 cases with isolated small foci of localized SARS-CoV-2 placentitis, characterized by focal perivillous fibrin and intervillositis, which illustrate the early pathogenesis and suggest that infection may be contained in some cases. Two other placental lesions were more common in mothers with COVID-19, high-grade maternal vascular malperfusion in preterm deliveries and high-grade chronic villitis at term (5/5 cases tested of the latter were negative by IHC for SARS-CoV-2). Additional investigation of diffuse and localized SARS-CoV-2 placentitis by IHC showed loss of BCL-2, C4d staining in surrounding villi, and an early neutrophil-predominant intervillous infiltrate that later became dominated by monocyte-macrophages. We propose a model of focal infection of syncytiotrophoblast by virally infected maternal leukocytes leading to loss of BCL-2 and apoptosis. Infection is then either contained by surrounding fibrinoid (localized) or initiates waves of aponecrosis and immune activation that spread throughout the villous parenchyma (diffuse).

妊娠期感染 2019 冠状病毒病 (COVID-19) 与早产和先兆子痫有关。一种不太常见且未被充分认识的并发症是广泛的胎盘感染，它与高围产期发病率和死亡率相关。与这种感染相关的病变频率、早期发病机制和范围尚不清楚。我们对在我们的卫生系统内分娩的所有患有 COVID-19 的母亲 (n=271) 进行了一项基于人群的胎盘病理学研究，研究为期 18 个月。根据 SARS-CoV-2 刺突蛋白的典型组织学和免疫组织化学 (IHC) 染色定义，弥漫性严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 胎盘炎的总体患病率为 14.8/1000，但增加至 59/1000。 1000 例早产。我们还发现了 3 例局部 SARS-CoV-2 胎盘炎的孤立小病灶，其特征是局灶性绒毛周纤维蛋白和绒毛间炎，这说明了早期发病机制，并表明某些病例中可能存在感染。另外两种胎盘病变在患有 COVID-19 的母亲中更为常见，即早产时的严重母亲血管灌注不良和足月时的严重慢性绒毛炎（后者的 5/5 例检测结果为 SARS-CoV-2 IHC 阴性） ）。通过 IHC 对弥漫性和局限性 SARS-CoV-2 胎盘炎进行的进一步研究显示，周围绒毛中 BCL-2、C4d 染色缺失，以及早期以中性粒细胞为主的绒毛间浸润，后来以单核巨噬细胞为主。我们提出了一种病毒感染的母体白细胞对合体滋养层进行局部感染的模型，导致 BCL-2 丢失和细胞凋亡。然后，感染要么被周围的纤维蛋白样所抑制（局部），要么引发一波波坏死和免疫激活，并扩散到整个绒毛实质（弥漫性）。