Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2

Abstract

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

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

“…This uniformity is in marked contrast to placentas from neonates who are not infected after delivery to mothers with COVID-19. 49 Placentas from uninfected infants show a wide spectrum of placental findings, including lesions representing maternal vascular malperfusion, fetal vascular malperfusion, inflammatory lesions including chorioamnionitis, funisitis and villitis, and in some cases, they may not have any specific pathology findings. 49,50 Chronic histiocytic intervillositis is an inflammatory lesion of the placenta first identified by Labarre and Mullen in 1987, who initially termed it massive chronic intervillositis.…”

“…49 Placentas from uninfected infants show a wide spectrum of placental findings, including lesions representing maternal vascular malperfusion, fetal vascular malperfusion, inflammatory lesions including chorioamnionitis, funisitis and villitis, and in some cases, they may not have any specific pathology findings. 49,50 Chronic histiocytic intervillositis is an inflammatory lesion of the placenta first identified by Labarre and Mullen in 1987, who initially termed it massive chronic intervillositis. 51 Referred to by a variety of differing terms in the medical literature, chronic histiocytic intervillositis has remained a condition of unknown etiology that has a high rate of recurrence and association with poor obstetric outcomes that include miscarriage, fetal demise, intrauterine growth restriction, and preterm delivery.…”

Clinical characteristics and outcomes of pregnant women with COVID-19 and the risk of vertical transmission: a systematic review

“…About a decade ago, the limited publications on pregnant women with SARS reported no evidence of vertical transmission [ 3 , 54 ]. Here, we included some single-center studies to summarize the possibility of vertical transmission of COVID-19 [ 30 , 31 , 47 , 55 – 58 ].…”

“…It is believed that pregnant women are more susceptible to virus infections due to immunologic and anatomic alterations [ 2 ]. Pregnant women with severe acute respiratory syndrome (SARS) or middle east respiratory syndrome (MERS) have serious adverse outcomes, such as maternal deaths and premature births, while no evidence of vertical transmission has been found [ 3 ]. As more articles have described the clinical characteristics and outcomes of pregnant women with COVID-19, our understanding of how COVID-19 may influence pregnant women continues to improve.…”

Is There an Effect of Fetal Mesenchymal Stem Cells in the Mother–Fetus Dyad in COVID-19 Pregnancies and Vertical Transmission?

“…The sampling of amniotic fluid could have provided an indication that vertical transmission might have occurred. A few studies investigated SARS-CoV-2-positive placental sampling to document direct viral involvement or vertical transmission ( Alamar et al, 2020 ; Schwartz and Morotti, 2020 ; Smithgall et al, 2020 ; Taglauer et al, 2020 ). Although there have been case reports of histomorphologic evidence of maternal/fetal vascular malperfusions ( Smithgall et al, 2020 ), there is still no concrete proof that SARS-CoV-2 placental invasion may lead to fetal pathology.…”