Chronic Histiocytic Intervillositis with Trophoblast Necrosis are Risk Factors Associated with Placental Infection from Coronavirus Disease 19 (COVID-19) and Intrauterine Maternal-Fetal Systemic Acute Respiratory Coronavirus 2 (SARSCoV-2) Transmission in Liveborn and Stillborn Infants.

Schwartz, David A; Baldewijns, Marcella; Benachi, Alexandra; Bugatti, Mattia; Collins, Rebecca R J; De Luca, Danièle; Facchetti, Fabio; Linn, Rebecca L; Marcelis, Lukas; Morotti, Denise; Morotti, Raffaella; Parks, W Tony; Patanè, Luisa; Prevot, Sophie; Pulinx, Bianca; Rajaram, Veena; Strybol, David; Thomas, Kristen; Vivanti, Alexandre J

CONTEXT Increasing numbers of neonates with systemic acute respiratory coronavirus 2 (SARS-CoV-2) infection are occurring, and in a small number there are reports of intrauterine infection. OBJECTIVE To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. DESIGN Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2 - liveborn neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology; and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2. RESULTS In placentas from all 6 liveborn neonates acquiring SARS-CoV-2 via transplacental transmission the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/terminated infants had placental pathology findings that were similar including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis and syncytiotrophoblast necrosis. CONCLUSIONS Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompany SARS-CoV-2 infection of syncytiotrophoblast in liveborn and stillborn infants. Their coexistence in all placentas from liveborn infants acquiring their infection prior to delivery indicates that that these findings constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARS-CoV-2, and potential future studies, are discussed.