Adverse Fetal Outcomes and Histopathology of Placentas Affected by COVID-19: A Report of Four Cases

Abstract

Coronavirus disease 2019 (COVID-19) has had significant impacts on mothers and neonates. In this report, we present four unique cases of COVID-19 infections in pregnancy and its effects on the mother, fetus, and placenta. Four mothers presented to the hospital during their pregnancy. Each had tested COVID-19-positive 1-29 days prior to admission. Gestational age ranged from 16 weeks six days to 36 weeks six days. Three of the four cases resulted in fetal demise or infant expiration. The common finding among all four cases was pathologic changes in the placenta. Most of the placentas were small for gestational age and had extensive villous infarction. There was also histiocytic intervillositis with villous necrosis and perivillous fibrin deposition. The placentas demonstrated positive staining of syncytiotrophoblasts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1 subunit protein. SARS-CoV-2 RNA was detected in tissue samples of two of the fetuses demonstrating vertical transmission. A higher incidence of severe COVID-19 disease course has been observed in pregnant women. Prior to the SARS-CoV-2 pandemic, chorionic histiocytic intervillositis of the placenta was rarely seen, and mostly of unknown etiology. The increase in placental fibrin levels results in decreased maternal placenta blood flow ensuing hypoxic stress in the fetus. Intrauterine hypoxia has been associated with alterations in brain structure and function resulting in defects in motor skills, cerebral palsy, decreased brain weight, schizophrenia, and other forms of cognitive impairment.

Placental inflammation in a fetal demise of a SARS-CoV-2-asymptomatic, COVID-19-unvaccinated pregnant woman: a case-report

“…We identified CD68 + macrophages in the chorionic plate, chorionic villi, and decidua basalis. Other reports have identified macrophages in the intervillous space of the chorionic villi in SARS-CoV-2-associated fetal demises, consistent with one criterion of the SARS-CoV-2 placentitis triad [ 6 , 14 , 17 , 18 ]. We additionally reported the presence of other immune cells, such as neutrophils, plasma cells, CD56 + NK cells and a few CD8 + T lymphocytes, which are implicated in antiviral responses, at sites of placental inflammation.…”

“…We additionally reported the presence of other immune cells, such as neutrophils, plasma cells, CD56 + NK cells and a few CD8 + T lymphocytes, which are implicated in antiviral responses, at sites of placental inflammation. Most cases reported the localization of SARS-CoV-2 spike and nucleocapsid antigens in syncytiotrophoblasts [ 9 , 19 ], cytotrophoblasts [ 19 ], within villous stromal cells including Hofbauer cells and villous capillary endothelial cells [ 20 , 21 ], and on the maternal side of the placenta [ 18 , 21 ]. We detected the SARS-CoV-2 nucleocapsid in both maternal decidual cells and fetal stromal cells of the chorion and chorionic villi, consistent with the sites of inflammation.…”

SARS-CoV-2 Infection in Late Pregnancy and Childbirth from the Perspective of Perinatal Pathology

“…The subsequent reports confirmed that the histopathological triad of SP was robust and reliable, facilitating the recognition of new cases of SARS-CoV-2 infection in the placenta. The term SP has become universally accepted [24,[36][37][38][39][40][41].…”

“…The inflammatory infiltrate in SP is patchy and rather scarce and, besides histiocytes, contains various numbers of neutrophils and lymphocytes [16,24,35]. In addition, unlike in CHI, PVFD in SP is marked and frequently massive, occupying more than 25% of the placental disc (and greater than 75% in cases of intrauterine fetal demise [38,41]). Finally, SP is characterized by extremely pronounced trophoblast necrosis due to combined effects of the complement-mediated immunological damage of this cellular layer, direct viral cytopathic change, and associated apoptosis [16,24,35,42].…”

“…SP was first reported in association with wild-type SARS-CoV-2 [28] and continued to be reported in subsequent years, when new variants emerged [38,40,46,47]. Several authors have noted a "surge" in positive cases with the delta variant [39,41,47]; however, this may have been related to the improved diagnostics of SP by the time this variant prevailed.…”