Unique Severe COVID-19 Placental Signature Independent of Severity of Clinical Maternal Symptoms.

Marjolein F Husen,Irwin K M Reiss,Hein Bogers,Annemiek A Van Der Eijk,Liv Freeman,Philip L J Dekoninck,Pieter L A Fraaij,Marjolijn D Trietsch,Sam Schoenmakers,Robert M Verdijk,Marion P G Koopmans,Lotte E Van Der Meeren

doi:10.3390/v13081670

Abstract

Background: Although the risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. Methods: A prospective, longitudinal, multicentre, cohort study. All pregnant women presenting between April 2020 and March 2021 with a nasopharyngeal RT-PCR-confirmed SARS-CoV-2 infection were included. Around delivery, maternal, foetal and placental PCR samples were collected. Placental pathology was correlated with clinical maternal characteristics of COVID-19. Results: Thirty-six patients were included, 33 singleton pregnancies (n = 33, 92%) and three twin pregnancies (n = 3, 8%). Twenty-four (62%) placentas showed at least one abnormality. Four placentas (4/39, 10%) showed placental staining positive for the presence of SARS-CoV-2 accompanied by a unique combination of diffuse, severe inflammatory placental changes with massive perivillous fibrin depositions, necrosis of syncytiotrophoblast, diffuse chronic intervillositis, and a specific, unprecedented CD20+ B-cell infiltration. This SARS-CoV-2 placental signature seems to correlate with foetal distress (75% vs. 15.6%, p = 0.007) but not with the severity of maternal COVID-19 disease. Conclusion: We describe a unique placental signature in pregnant patients with COVID-19, which has not been reported in a historical cohort. We show that the foetal environment can be seriously compromised by disruption of placental function due to local, devastating SARS-CoV-2 infection. Maternal clinical symptoms did not predict the severity of the SARS-CoV-2-related placental signature, resulting in a lack of adequate identification of maternal criteria for pregnancies at risk. Close foetal monitoring and pregnancy termination in case of foetal distress can prevent adverse pregnancy outcomes due to COVID-19 related placental disease.

Highlights

COVID-19 in pregnancy is associated with increased severe maternal morbidity and mortality as well as adverse pregnancy outcome [1,2,3]
We described a unique placental signature with a specific presence of CD20+ B-cells clustering around the necrotic syncytiotrophoblast combined with chronic intervillositis and perivillous fibrin depositions, in pregnant patients with COVID-19 not seen in historic
Placental SARS-CoV-2 positivity was characterised by an unprecedented combination of chronic intervillositis, massive perivillous fibrin depositions, necrotic syncytiotrophoblast, chronic villitis and the presence of a unique, distinctive CD20+ B-cell infiltrate (Figure 1)

Summary

Introduction

COVID-19 in pregnancy is associated with increased severe maternal morbidity and mortality as well as adverse pregnancy outcome [1,2,3]. Perinatal risks and pregnancy outcomes appear to be related to the severity of the illness in women with COVID-19 [1,4,5]. Despite a limited risk of vertical transmission (with probable cases estimated to be around 3–4%), the prevalence of placental infection in women with COVID-19 reportedly is up to 7.7–21% [6,7] and its clinical consequences should be considered. The risk for transplacental transmission of SARS-CoV-2 is rare, placental infections with adverse functional consequences have been reported. This study aims to analyse histological placental findings in pregnancies complicated by SARS-CoV-2 infection and investigate its correlation with clinical symptoms and perinatal outcomes. We want to determine which pregnancies are at-risk to prevent adverse pregnancy outcomes related to COVID-19 in the future. Placental pathology was correlated with clinical maternal characteristics of COVID-19

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Conclusion