COVID-19-associated pathological changes in placentae of third-trimester pregnant women

Abstract

Background and aim Recently, many instances of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [coronavirus disease 2019 (COVID-19)] placental invasion in late pregnancy have been reported, and this is still not completely clear. Controversy data are sequentially published, so more studies are needed to investigate placental pathology as it gives vital information on placental changes, mechanisms of maternal–fetal infection transmission, and viral effects on the placenta as inflammatory or vascular changes. We aimed to find out the placental pathological changes in term placentae and to detect SARS-CoV-2 RNA in specimens fixed in formalin and embedded in paraffin. Patients and methods A total of 30 placentae were obtained from COVID-19-infected pregnant women. They were examined for pathological changes by histopathology; immunohistochemistry for CD3, CD20, CD15, CD68, angiotensin-converting enzyme 2, cytokeratin, and PDL-1; and reverse transcription-PCR to recognize viral RNA. Results According to the COVID-19 status at the delivery time, four groups were identified. Group 1 (12 patients with COVID-19 at the delivery time) showed chronic villitis and placental maternal and fetal malperfusion. Group 2 (seven cases that turned negative by PCR of the nasopharyngeal swab prior to delivery by 5–8 days) showed maternal malperfusion but no villitis. Both groups were SARS-CoV-2 RNA positive by PCR of the nasopharyngeal swab. Group 3 (five cases that turned negative 1 day before delivery) showed maternal–fetal malperfusion and mild chronic subchorionitis and deciduitis. Only three had SARS-CoV RNA. Group 4 (six cases with a persistent negative swab for 20 days before delivery) showed focal villitis (much less than other groups) and maternal malperfusion. Only two had SARS-CoV-2 RNA. Immunophenotyping of cases in the four groups detected mixed inflammatory infiltrate with variable diffuse angiotensin-converting enzyme 2 immunostaining of villus and extravillous trophoblasts. Cytokeratin staining detected thinning and discontinuity of syncytiotrophoblast and strong PD-L1 expression was seen in villitis areas. Conclusion SARS-CoV-2-positive women exhibited a diverse range of results; thus, pregnant women should not be considered a homogeneous group as outcomes are dependent on a multitude of interdependent circumstances.