Chronic Histiocytic Intervillositis With Trophoblast Necrosis Is a Risk Factor Associated With Placental Infection From Coronavirus Disease 2019 (COVID-19) and Intrauterine Maternal-Fetal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission in Live-Born and Stillborn Infants

Abstract

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.

Fetal and placental infection with SARS‐CoV‐2 in early pregnancy

“…Recently, Schwartz and cols. 15 findings underpin that the CHI could be a relevant mechanism for SARS-CoV-2 vertical transmission. Potentially, placental damage by necrosis of syncytiotrophoblasts may be associated with the viral cytotoxicity and ischemia produced by malperfusion from CHI.…”

“…Although vertical transmission of coronavirus is a rare event, it was documented in the third trimester of pregnancy by (1) the presence of anti-SARS-CoV-2 IgM antibodies in a neonate from a COVID-19 pregnant woman, 6 (2) detection of the virus in the placenta, [10][11][12][13][14][15] (3) neonatal viremia associated with COVID-19 and neurological symptoms, (4) SARS-CoV-2 infection of the placenta and fetal intravascular monocytes, 14 and recently, (5) the detection of SARS-CoV-2 RNA in fetal lung samples obtained by needle puncture. 17 Together with previous reports, our findings support that in utero transmission of SARS-CoV-2, although a rare event, is actually possible in early pregnancy.…”

Effect of SARS‐CoV‐2 infection during the second half of pregnancy on fetal growth and hemodynamics: A prospective study

“…To the best of our knowledge, this is the first study investigating infection. [11][12][13] In this study, placental pathology was not analyzed, so we cannot address this question. Moreover, outside SARS-CoV-2 infection, every condition leading to maternal vascular hypoperfusion is potentially associated with higher risk of impaired placental function, growth restriction, and stillbirth.…”

“…27 Features of fetal and maternal vascular malperfusion characterized by decidual arteriopathy with atherosis, fibrinoid necrosis, and mural hypertrophy of decidual arterioles have been described in placentas from pregnant women with SARS-CoV-2 infection. [11][12][13] In this study, placental pathology was not analyzed, so we cannot address this question. Moreover, outside SARS-CoV-2 infection, every condition leading to maternal vascular hypoperfusion is potentially associated with higher risk of impaired placental function, growth restriction, and stillbirth.…”

“…9,10 This assumption has been subsequently strengthened by the reported increased prevalence of signs of decidual arteriopathy in pregnant women with SARS-CoV-2 infection, suggesting a potential connection between infection and impaired placental function. [11][12][13] On this basis, we hypothesized that placental changes due to SARS-CoV-2 infection may lead to impaired fetal growth in these pregnancies and alter fetal hemodynamics.…”