Defining Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Placentitis

Abstract

Context.–Case reports and rare case series have demonstrated variable placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In rare small studies demonstrating infection of the placental parenchyma, histologic manifestations have included variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and syncytiotrophoblast necrosis. Objective.–To characterize the placental pathological features of SARS-CoV-2 infected placentas, irrespective of fetal-maternal transmission, and to examine the frequency of C4d activation in such cases. Design.–Retrospective study of seven placentas from mothers with active SARS-CoV-2 infection and placental infection as demonstrated by RNA in situ hybridization. Results.–Six placentas were from live-born neonates (5 singletons, 1 non-fused diamniotic-dichorionic twin placenta), and one was from a stillbirth. Five of the eight neonates (including the stillbirth) tested negative for SARS-CoV-2, and all were negative for neonatal infection. The remaining three neonates were well at time of discharge. All placentas were positive for SARS-CoV-2 infection by RNA in situ hybridization and demonstrated variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. Three cases demonstrated features of fetal vascular malperfusion. CD68 highlighted intervillous histiocytes. C4d expression was present along the villous borders in 6 of 7 cases. Conclusions.–SARS-CoV-2 placentitis is defined by the triad of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. The features may occur in cases without confirmed transplacental transmission. The damage caused by SARS-CoV-2 placentitis is likely mediated by complement activation.

COVID-19 Infection in Pregnancy: PCR Cycle Thresholds, Placental Pathology, and Perinatal Outcomes

“…In contrast, several studies have investigated the placenta of infected mothers and have found the formation of fibrin layers mirroring a massive perivillous fibrin deposition in placentas positive for SARS-CoV-2 RNA by in situ hybridization. Furthermore, SARS-CoV-2 infection of the placenta was shown to be associated with a combination of histopathological features, now termed SARS-CoV-2 placentitis, which include histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis [9,10,24]. Although we did not study SARS-CoV-2 infection of the placenta by in situ hybridization or immunohistochemistry, these findings underpin our results.…”

Response to “Diffuse trophoblast damage is the hallmark of SARS-CoV-2-associated fetal demise.”

“…More studies are needed investigating the impact of the virus and its variants as well as exploring the placental effects as these may provide explanations into the mechanisms of trophoblast destruction. We as well as others have demonstrated evidence of C4d deposition along the trophoblastic surface of villi, suggesting complement fixation along villi borders may lead to its destruction and thus, theoretically, corticosteroids could be administered prenatally in attempt to lessen the placental response to infection 21 – 23 . However, additional studies are needed at this time, particularly to determine if other mechanisms are also at play.…”

“…One point that we wish to clarify and highlight is that diffuse trophoblast damage is a hallmark of placental SARS-CoV-2 infection, not a hallmark of SARS-CoV-2-associated intrauterine fetal demise per se, even when found in a diffuse pattern. In a recent publication describing our institution’s experience, we found that of seven placentas with SARS-CoV-2 infection, six were from live-born neonates 21 . We found that our cases demonstrated characteristic pathologic alterations, which consisted of a histopathologic triad of histiocytic (and neutrophilic) intervillositis, perivillous fibrin deposition, and trophoblast necrosis, termed officially as “SARS-CoV-2 placentitis.” In addition, outside of our published results, we performed a search of our pathology information system for a more recent period (January to September 2021) and discovered that 14 of 26 cases of SARS-CoV-2 placentitis resulted in livebirths.…”

Intrauteriner Fruchttod bei massiver SARS-CoV-2-assoziierter („severe acute respiratory syndrome coronavirus 2“) plazentarer maternaler Malperfusion im Rahmen einer SARS-CoV-2-Plazentitis

“…Wir stellen eine Plazenta der 31. SSW eines IUFT vor, bei der sich mittels der Trias aus ausgedehnten intervillösen Fibrinablagerungen, einer CHI und Trophoblastnekrosen die Diagnose einer SARS-CoV-2-Plazentitis stellen lässt [ 19 ]. Dies führte zu einer ausgeprägten maternalen vaskulären Malperfusion in Form einer subtotalen (fast 95 %) Parenchyminfarzierung sowie intervillösen Thromben und zusätzlich einer fokalen fetalen vaskulären Malperfusion.…”

“…Erst in den letzten Monaten wird die Kombination aus massiven intervillösen Fibrinabscheidungen, Trophoblastnekrose und einer CHI unter dem Begriff der SARS-CoV-2-Plazentitis als COVID-19-typischer Plazentabefund bei einer akuten Infektion beschrieben [ 6 , 19 ].…”