COVID-19 & differential effects in twins: Insights from Placenta Pathology

Abstract

Introduction: COVID-19 has been associated with several adverse pregnancy outcomes, including perinatal loss. Differential effects of COVID-19 in a twin pregnancy may provide unique insights into virus-placental interactions. We present a case of perinatal loss of a female fetus with survival of the male co-twin in a pregnancy complicated by COVID-19 and premature delivery.

Methods: Viral detection methods recommended by the NICHD task force were used to identify SARS-CoV-2 and its viral receptors in the placentas and fetal tissue (Antoun et al., 2020) [1] RESULTS: Compared with the surviving twin, we found a more severe intervillous necrosis and a relatively low detection of ACE2 membranous expression in the syncytiotrophoblasts of the female twin that succumbed.

Discussion: The interactions of SARS-CoV-2 and ACE2 at the maternal fetal interface within the placenta may play a significant role in perinatal loss, and the effects of fetal sex and gestational age at time of infection need to be explored further.

Fig. 1

Cross sections of placenta parenchyma. Both placentas show tan, firm abnormal tissue (red arrows); only scant normal appearing dark red and spongy parenchyma is seen (green arrows).

Fig. 2

Placenta from twin A. A: low power shows agglutinated villi with obliterated Intervillous spaces (4x). B: Higher power shows trophoblastic necrosis (red arrows), Inflammatory cell infiltrates in intervillous spaces (green arrows), and fibrin (blue arrows). C: Immunohistochemistry with CD68 demonstrates histiocytic intervillositis (brown stain). D: Immunohistochemistry with antibody to COVID-19 nucleocapsid protein shows strong Immunoreactivity in syncytialtrophoblasts (brown stain). E: RNA ISH using probes for COVID-19 spike protein exhibits strong signals in syncytialtrophoblasts (brown granular Stains). F: Immunostain for ACE2 receptors illustrates positive staining within viable Syncytiotrophoblast (red arrows), while non-viable villi without apparent signal (green Arrow, background stain). B to F: 20x

Fig. 3

Real time PCR of 4 patient samples are all positive for COVID-19 signals (ORF1ab, N gene, and S gene).Control signal MS2 is not amplified.A: Twin A placenta. Cycle threshold (Ct) 14 B: Twin B placenta. Ct 14 C: Fetal lung. Ct 33 D: Fetal heart. Ct 34.