key: cord-0821222-qvzij2dp
authors: Moriarty, Kristen; Yu, Mingfu; Hussain, Naveed; Zgutka, Kinga; Sanders, M. Melinda; Harigopal, Malini; Wang, Jianhui; Wang, Xi; Hui, Pei; Liu, Chen; Sink, David; Shields, Andrea
title: COVID-19 & differential effects in twins: Insights from Placenta Pathology
date: 2022-05-20
journal: Placenta
DOI: 10.1016/j.placenta.2022.05.014
sha: 26cc19ef73354dc6089ab9ca2d8cd3957d1e9412
doc_id: 821222
cord_uid: qvzij2dp

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.

Unfortunately, she presented prior to the FDA authorization of monoclonal antibodies to treat 24 mild to moderate COVID-19 patients. Her cervical exam remained unchanged at 48 hours and 25 medical interventions were discontinued. Within four hours of discontinuing medical 26 interventions, a cesarean delivery under general anesthesia was performed due to rapid 27 progression in preterm labor, fetal malpresentation and systemic anticoagulation. The neonatal 28 intensive care unit (NICU) team was present for delivery. Twin A, a female, received positive 29 pressure ventilation (PPV), followed by intubation, chest compressions, endotracheal and 30 intravascular epinephrine doses, and normal saline boluses due to an absent heart rate. Heart 31 rate remained undetectable, and resuscitation was stopped at 23 minutes of life. She had no 32 signs of tissue maceration. At birth, twin B, a male, had poor respiratory effort, and received 33 PPV followed by intubation. After 24 hours of life, he was extubated and placed on non-invasive 34 PPV but required re-intubation 12 hours later. His SARS-CoV-2 PCR testing at 24 and 48 hours of 35 life was negative. His neonatal course was significant for ampicillin-resistant E-coli sepsis at 10 36 days of life and acquired cytomegalovirus infection at one month. He was discharged home 37 with moderate bronchopulmonary dysplasia and stage 1 retinopathy of prematurity. 38

The maternal postpartum course was uncomplicated. She recovered from her COVID-19 39 infection and was discharged on the second postoperative day. She was diagnosed with 40 postpartum adjustment disorder and referred for mental health counseling. Patient consent 41 was obtained for the presentation of this case. PCR results of all tissues tested were positive for SARS-CoV-2, which included 2 FFPE 104 blocks from twin placentas, and the fetal lung and heart of twin A. Cycle threshold (Ct) was 105 negatively associated with the viral load (Figure 3a to 3d) . 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. 

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