Severe Acute Respiratory Syndrome Coronavirus 2 Placental Infection and Inflammation Leading to Fetal Distress and Neonatal Multi-Organ Failure in an Asymptomatic Woman

Schoenmakers, Sam; Snijder, Pauline M.; Verdijk, Robert M.; Kuiken, Thijs; Kamphuis, Sylvia; Koopman, Laurens P.; Krasemann, Thomas; Rousian, Melek; Broekhuizen, Michelle; Steegers, Eric A.P.; Koopmans, Marion; Fraaij, Pieter L. A.; Reiss, Irwin K M

doi:10.1093/jpids/piaa153

Cited by 71 publications

(76 citation statements)

References 29 publications

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“…16,31,32 Since then, additional similar cases with these findings have been reported. [33][34][35][36][37][38] Hofbauer cells are fetal macrophages that are normally present within chorionic villi from as early as 18 days gestation up to delivery. Located within the chorionic villous stroma, in close proximity to both the trophoblast layer as well as the villous capillaries, Hofbauer cells are in an optimal position to respond to pathogenic organisms potentially crossing the maternalfetal interface.…”

Section: Introductionmentioning

confidence: 99%

Hofbauer Cells and COVID-19 in Pregnancy

Schwartz

Baldewijns

Benachi

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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Context.– Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases including HIV and Zika virus, but their involvement in SARS-CoV-2 in unknown. Objective.– To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.– Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast and other fetal-derived cells. Results.– Chronic histiocytic intervillositis and trophoblast necrosis was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.– SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

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Section: Introductionmentioning

confidence: 99%

Hofbauer Cells and COVID-19 in Pregnancy

Schwartz

Baldewijns

Benachi

et al. 2021

Archives of Pathology &Amp; Laboratory Medicine

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“…The current study aims to determine if placental infection by SARS-CoV-2 can be predicted based on the severity of maternal clinical presentation of COVID-19 and to identify pregnancy at-risk for adverse foetal outcomes. The reported SARS-CoV-2 associated histological changes in the placenta are chronic intervillositis, chronic villitis, massive perivillous fibrin depositions and syncytiotrophoblast damage resulting in necrosis [ 7 , 20 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], which can limit the essential gas- and nutrient exchange at the maternal-foetal interface, necessary for foetal survival [ 24 ]. The remaining functional placental interface relative to the amount of damaged or fibrin-occluded interface will determine the level of effect on foetal growth and development.…”

Section: Introductionmentioning

confidence: 99%

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

Husen

Meeren

Verdijk

et al. 2021

Viruses

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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.

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“…In addition to all 11 placentas having these concurrent abnormalities, most placentas also showed increased fibrin deposition, including some with massive perivillous fibrin deposition [27]. The simultaneous occurrence of these abnormalities was beyond coincidence and has subsequently been reported from additional infected placentas [37][38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 93%

Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

Schwartz

Bugatti

Santoro

et al. 2021

JDB

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A subset of placentas from pregnant women having the SARS-CoV-2 infection have been found to be infected with the coronavirus using molecular pathology methods including immunohistochemistry and RNA in situ hybridization. These infected placentas can demonstrate several unusual findings which occur together—chronic histiocytic intervillositis, trophoblast necrosis and positive staining of the syncytiotrophoblast for SARS-CoV-2. They frequently also have increased fibrin deposition, which can be massive in some cases. Syncytiotrophoblast is the most frequent fetal-derived cell type to be positive for SARS-CoV-2. It has recently been shown that in a small number of infected placentas, villous stromal macrophages, termed Hofbauer cells, and villous capillary endothelial cells can also stain positive for SARS-CoV-2. This report describes a placenta from a pregnant woman with SARS-CoV-2 that had chronic histiocytic intervillositis, trophoblast necrosis, increased fibrin deposition and positive staining of the syncytiotrophoblast for SARS-CoV-2. In addition, molecular pathology testing including RNAscope and immunohistochemistry for SARS-CoV-2 and double-staining immunohistochemistry using antibodies to E-cadherin and GATA3 revealed that cytotrophoblast cells stained intensely for SARS-CoV-2. All of the cytotrophoblast cells that demonstrated positive staining for SARS-CoV-2 were in direct physical contact with overlying syncytiotrophoblast that also stained positive for the virus. The pattern of cytotrophoblast staining for SARS-CoV-2 was patchy, and there were chorionic villi having diffuse positive staining of the syncytiotrophoblast for SARS-CoV-2, but without staining of cytotrophoblast. This first detailed description of cytotrophoblast involvement by SARS-CoV-2 adds another fetal cell type from infected placentas that demonstrate viral staining.

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Severe Acute Respiratory Syndrome Coronavirus 2 Placental Infection and Inflammation Leading to Fetal Distress and Neonatal Multi-Organ Failure in an Asymptomatic Woman

Cited by 71 publications

References 29 publications

Hofbauer Cells and COVID-19 in Pregnancy

Hofbauer Cells and COVID-19 in Pregnancy

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

Molecular Pathology Demonstration of SARS-CoV-2 in Cytotrophoblast from Placental Tissue with Chronic Histiocytic Intervillositis, Trophoblast Necrosis and COVID-19

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