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1.
Placenta ; 126: 209-223, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1937083

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Female , Humans , Placenta/metabolism , Pregnancy , SARS-CoV-2 , Trophoblasts/pathology
2.
Placenta ; 126: 125-132, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1914907

ABSTRACT

INTRODUCTION: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. METHODS: We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. RESULTS: The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (≥37 weeks), and gestational age at delivery did not differ between the SARS-CoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. DISCUSSION: SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Antibodies, Viral , Female , Humans , Immunoglobulin G , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2 , Trophoblasts/pathology
3.
Am J Surg Pathol ; 46(2): 258-267, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1778992

ABSTRACT

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.


Subject(s)
Placenta Diseases/pathology , Trophoblastic Neoplasms/pathology , Trophoblasts/pathology , Uterine Neoplasms/pathology , Adolescent , Adult , Biopsy , Diagnosis, Differential , Female , Fumarate Hydratase/analysis , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Middle Aged , Multienzyme Complexes/analysis , Placenta Diseases/metabolism , Predictive Value of Tests , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Progesterone Reductase/analysis , Steroid Isomerases/analysis , Trophoblastic Neoplasms/chemistry , Trophoblasts/chemistry , United States , Uterine Neoplasms/chemistry , Young Adult
6.
Bull Exp Biol Med ; 172(1): 85-89, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1520386

ABSTRACT

We performed a comparative morphological analysis of placental villi in parturient women with mild and moderate COVID-19 infection. The area and perimeter of terminal villi, their capillaries, and syncytiotrophoblast were assessed on immunohistochemical preparations with antibodies to CD31 using an image analysis system; the parameters of fetal vascular component in the placental villi were also assessed. Changes in the studied parameters differed in parturient women with mild and moderate COVID-19 infection. The observed increase in the total perimeter with a simultaneous decrease in the total capillary area and the degree of vascularization of the placental villi in parturient women with COVID-19 indicates impairment of circulation in the fetal compartment and the development of placental hypoxia, which can be the cause of unfavorable neonatal outcomes.


Subject(s)
COVID-19/pathology , Chorionic Villi/pathology , Pregnancy Complications, Infectious/pathology , SARS-CoV-2/pathogenicity , Trophoblasts/pathology , Adult , COVID-19/virology , Chorionic Villi/blood supply , Chorionic Villi/virology , Female , Fetus , Humans , Immunohistochemistry , Parturition/physiology , Pregnancy , Pregnancy Complications, Infectious/virology , SARS-CoV-2/growth & development , Severity of Illness Index , Trophoblasts/virology
7.
Arch Pathol Lab Med ; 145(11): 1328-1340, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1485410

ABSTRACT

CONTEXT.­: 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 SARS-CoV-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 is 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 were present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4 of 22 placentas (18.2%). Villous capillary endothelial staining was positive in 2 of 22 cases (9.1%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21 of 22 placentas (95.5%). Hofbauer cell hyperplasia was present in 3 of 22 placentas (13.6%). In the 7 cases having documented transplacental infection of the fetus, 2 (28.6%) 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.


Subject(s)
COVID-19/transmission , COVID-19/virology , Infectious Disease Transmission, Vertical , Macrophages/virology , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Adult , COVID-19/immunology , COVID-19/pathology , Cell Proliferation , Endothelium/pathology , Endothelium/virology , Female , Humans , Hyperplasia/pathology , Hyperplasia/virology , Infant, Newborn , Macrophages/pathology , Macrophages/physiology , Male , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Retrospective Studies , SARS-CoV-2/immunology , Stillbirth , Trophoblasts/pathology , Trophoblasts/virology
8.
Diagn Pathol ; 16(1): 88, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1448245

ABSTRACT

INTRODUCTION: COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, is a severe systemic thrombotic syndrome that emerged in 2019, with an ensuing pandemic. To evaluate the impact of this disease on placental tissue and perinatal outcome, histological, immunohistochemical and ultrastructural analyses of placental tissue were performed for five cases of pregnant women with COVID-19. CASE REPORTS: All five pregnant women in this series developed COVID-19 in late pregnancy. Two patients experienced respiratory distress, and computed tomography revealed signs of pneumonia, with bilateral involvement, multiple lobular and subsegmental areas of consolidation and ground-glass opacities. Histological studies of placental tissue revealed the presence of slight signs of maternal vascular underperfusion (MVUs) or foetal vascular underperfusion (FVUs) lesions and mild inflammatory lesions. CD15 immunoreactivity in the placental tissue was low in all cases, demonstrating that in these cases there was not severe foetal hypoxia/asphyxia risk for newborns or distal vascular immaturity. In all cases examined, ultrastructural analyses showed spherical-like coronavirus particles with an electron intermediate-density core as well as projections from the surface as spike-like structures in the syncytiotrophoblasts. At term, all of the women delivered newborns who were negative for SARS-CoV-2 by nasopharyngeal testing in their first day of life. All newborns were exclusively breastfed and were discharged on the 3rd day of life. CONCLUSIONS: In conclusion, placental patterns in pregnancy due to COVID-19 in the late stage of gestation indicate no evidence of vertical trans-placental SARS-CoV-2 transmission or a significant impact on the perinatal outcome of newborns, in both mild and more severe cases.


Subject(s)
COVID-19/diagnostic imaging , Infectious Disease Transmission, Vertical , Pandemics , Pregnancy Complications, Infectious , SARS-CoV-2/physiology , Adult , COVID-19/epidemiology , COVID-19/pathology , COVID-19/virology , Female , Humans , Infant, Newborn , Placenta/diagnostic imaging , Placenta/pathology , Placenta/virology , Pregnancy , Pregnancy Outcome , Tomography, X-Ray Computed , Trophoblasts/pathology , Trophoblasts/virology
9.
Viruses ; 13(8)2021 08 23.
Article in English | MEDLINE | ID: covidwho-1367928

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.


Subject(s)
COVID-19/pathology , Placenta Diseases/pathology , Placenta/pathology , Pregnancy Complications, Infectious/pathology , Adult , COVID-19/physiopathology , COVID-19/virology , Female , Fetal Distress/physiopathology , Humans , Longitudinal Studies , Placenta/physiopathology , Placenta/virology , Placenta Diseases/physiopathology , Placenta Diseases/virology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Trophoblasts/pathology
10.
Placenta ; 112: 97-104, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1333705

ABSTRACT

INTRODUCTION: Pregnant women with covid-19 are more likely to experience preterm birth. The virus seems to be associated with a wide range of placental lesions, none of them specific. METHOD: We collected cases of Covid-19 maternal infection during pregnancy associated with poor pregnancy outcomes, for which we received the placenta. We studied clinical data and described pathological findings of placenta and post-mortem examination of fetuses. We performed an immunohistochemical study and RT-PCR of SARS-Cov-2 on placenta samples. RESULTS: We report 5 cases of poor fetal outcome, 3 fetal deaths and 2 extreme premature neonates, one with growth restriction, without clinical and biological sign of SARS-Cov-2 infection. All placenta presented massive perivillous fibrin deposition and large intervillous thrombi associated with strong SARS-Cov-2 expression in trophoblast and SARS-CoV-2 PCR positivity in amniotic fluid or on placenta samples. Chronic histiocytic intervillositis was present in 4/5 cases. Placental ultrasound was abnormal and the sFLT1-PIGF ratio was increased in one case. Timing between mothers' infection and the poor fetal outcome was ≤10 days in 4 cases. The massive placental damage are directly induced by the virus whose receptors are expressed on trophoblast, leading to trophoblast necrosis and massive inflammation in villous chamber, in a similar way it occurs in diffuse alveolar damage in adults infected by SARS-Cov-2. DISCUSSION: SARS-Cov-2 can be associated to a rare set of placental lesions which can lead to fetal demise, preterm birth, or growth restriction. Stronger surveillance of mothers infected by SARS-Cov-2 is required.


Subject(s)
COVID-19/complications , Placenta Diseases/etiology , Premature Birth/etiology , Stillbirth , Adult , COVID-19/diagnosis , COVID-19/pathology , Female , Fetal Death/etiology , France , Humans , Infant, Newborn , Male , Perinatal Death/etiology , Placenta/pathology , Placenta/virology , Placenta Diseases/diagnosis , Placenta Diseases/pathology , Placenta Diseases/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Premature Birth/pathology , Premature Birth/virology , SARS-CoV-2/physiology , Trophoblasts/pathology , Trophoblasts/virology
11.
Am J Pathol ; 191(9): 1610-1623, 2021 09.
Article in English | MEDLINE | ID: covidwho-1316372

ABSTRACT

Despite occasional reports of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy, the question of placental infection and its consequences for the newborn remain unanswered. Herein, we analyzed the placentas of 31 coronavirus disease 2019-positive mothers by reverse transcriptase PCR, immunohistochemistry, and in situ hybridization. Only one case of placental infection was detected, which was associated with intrauterine demise of the fetus. Differentiated primary trophoblasts were then isolated from nonpathologic human placentas at term, differentiated, and exposed to SARS-CoV-2 virions. Unlike for positive control cells Vero E6, the virus inside cytotrophoblasts and syncytiotrophoblasts or in the supernatant 4 days after infection was undetectable. As a mechanism of defense, we hypothesized that trophoblasts at term do not express angiotensin-converting enzyme 2 and transmembrane protease serine 2 (TMPRSS2), the two main host membrane receptors for SARS-CoV-2 entry. The quantification of these proteins in the placenta during pregnancy confirmed the absence of TMPRSS2 at the surface of the syncytium. Surprisingly, a transiently induced experimental expression of TMPRSS2 did not allow the entry or replication of the virus in differentiated trophoblasts. Altogether, these results underline that trophoblasts are not likely to be infected by SARS-CoV-2 at term, but raise concern about preterm infection.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19 , Gene Expression Regulation, Enzymologic , Placenta Diseases , Pregnancy Complications, Infectious , SARS-CoV-2/metabolism , Serine Endopeptidases/biosynthesis , Trophoblasts , Virus Internalization , Adult , COVID-19/enzymology , COVID-19/pathology , Female , Humans , Placenta Diseases/enzymology , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/enzymology , Pregnancy Complications, Infectious/pathology , Trophoblasts/enzymology , Trophoblasts/pathology
12.
Pediatr Dev Pathol ; 24(6): 581-584, 2021.
Article in English | MEDLINE | ID: covidwho-1285163

ABSTRACT

Placental infection by SARS-CoV-2 with various pathologic alterations reported. Inflammatory findings, such as extensive perivillous fibrin deposition and intervillous histiocytosis, have been postulated as risk factors for fetal infection by SARS-CoV-2. We describe the placental findings in a case of a 31-year-old mother with SARS-CoV-2 infection who delivered a preterm female neonate who tested negative for SAR-CoV2 infection. Placental examination demonstrated a small for gestational age placenta with extensive intervillous histiocytosis, syncytiotrophoblast karyorrhexis, and diffuse intervillous fibrin deposition. Immunohistochemical staining demonstrated infection of the syncytiotrophoblasts by SARS-CoV-2 inversely related to the presence of intervillous histiocytes and fibrin deposition. Our case demonstrates that despite extensive placental pathology, no fetal transmission of SARS-CoV-2 occurred, as well as postulates a relationship between placental infection, inflammation, and fibrin deposition.


Subject(s)
COVID-19/transmission , Fibrin/metabolism , Histiocytosis/pathology , Pregnancy Complications, Infectious/pathology , SARS-CoV-2/physiology , Adult , COVID-19/virology , Female , Histiocytosis/virology , Humans , Immunohistochemistry , Infant, Newborn , Placenta/pathology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/virology , Trophoblasts/pathology , Trophoblasts/virology
13.
Mod Pathol ; 34(9): 1704-1709, 2021 09.
Article in English | MEDLINE | ID: covidwho-1233700

ABSTRACT

Placental pathology in SARS-CoV-2-infected pregnancies seems rather unspecific. However, the identification of the placental lesions due to SARS-CoV-2 infection would be a significant advance in order to improve the management of these pregnancies and to identify the mechanisms involved in a possible vertical transmission. The pathological findings in placentas delivered from 198 SARS-CoV-2-positive pregnant women were investigated for the presence of lesions associated with placental SARS-CoV-2 infection. SARS-CoV-2 infection was investigated in placental tissues through immunohistochemistry, and positive cases were further confirmed by in situ hybridization. SARS-CoV-2 infection was also investigated by RT-PCR in 33 cases, including all the immunohistochemically positive cases. Nine cases were SARS-CoV-2-positive by immunohistochemistry, in situ hybridization, and RT-PCR. These placentas showed lesions characterized by villous trophoblast necrosis with intervillous space collapse and variable amounts of mixed intervillous inflammatory infiltrate and perivillous fibrinoid deposition. Such lesions ranged from focal to massively widespread in five cases, resulting in intrauterine fetal death. Two of the stillborn fetuses showed some evidence of SARS-CoV-2 positivity. The remaining 189 placentas did not show similar lesions. The strong association between trophoblastic damage and placenta SARS-CoV-2 infection suggests that this lesion is a specific marker of SARS-CoV-2 infection in placenta. Diffuse trophoblastic damage, massively affecting chorionic villous tissue, can result in fetal death associated with COVID-19 disease.


Subject(s)
COVID-19/complications , Fetal Death/etiology , Pregnancy Complications, Infectious/pathology , Trophoblasts/pathology , Adult , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/virology , SARS-CoV-2
16.
Hum Pathol ; 109: 69-79, 2021 03.
Article in English | MEDLINE | ID: covidwho-1036691

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was demonstrated in the placenta; however, the data on the prevalence of placental infection and associated histopathology are limited. To identify the frequency and features of SARS-CoV-2 involvement, we performed a clinicopathologic analysis of 75 placental cases from women infected at the time of delivery and 75 uninfected controls. Placental samples were studied with anti-SARS-CoV-2 immunohistochemistry and/or in situ hybridization. Positive results were confirmed by electron microscopy and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). During delivery, only one woman had symptoms of coronavirus disease 2019, six women reported previous symptoms, and 68 women were asymptomatic. All neonates tested negative for SARS-CoV-2 as per nasopharyngeal swab PCR results. Obstetric histories were unremarkable in 29 of 75 SARS-CoV-2-positive and 8 of 75 SARS-CoV-2-negative women. Placental examination was normal in 12 of 75 infected and 3 of 75 uninfected subjects, respectively. In the remaining cases, placental pathology correlated with obstetric comorbidities without significant differences between SARS-CoV-2-positive and SARS-CoV-2-negative women. SARS-CoV-2 was identified in one placenta of an infected, but asymptomatic, parturient. Viral staining was predominantly localized to the syncytiotrophoblast (STB) which demonstrated marked damage accompanied by perivillous fibrin deposition and mixed intervillositis. A significant decrease of viral titers was detected in the attached umbilical cord compared with the villous parenchyma as per qRT-PCR. SARS-CoV-2 is seldom identified in placentas of infected women. Placental involvement by the virus is characterized by STB damage disrupting the placental barrier and can be seen in asymptomatic mothers without evidence of vertical transmission.


Subject(s)
COVID-19/virology , Placenta/pathology , SARS-CoV-2/pathogenicity , Trophoblasts/pathology , Trophoblasts/virology , Adult , Female , Humans , In Situ Hybridization/methods , Placenta/virology , Pregnancy , RNA, Viral , Trophoblasts/chemistry , Viral Load
17.
Arch Pathol Lab Med ; 145(5): 517-528, 2021 05 01.
Article in English | MEDLINE | ID: covidwho-1006160

ABSTRACT

CONTEXT.­: The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection. OBJECTIVE.­: To characterize the placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection. DESIGN.­: Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2: live-born neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology, and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2. RESULTS.­: In placentas from all 6 live-born neonates acquiring SARS-CoV-2 via transplacental transmission, the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/terminated infants had placental pathology findings that were similar, including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis, and syncytiotrophoblast necrosis. CONCLUSIONS.­: Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompanies SARS-CoV-2 infection of syncytiotrophoblast in live-born and stillborn infants. The coexistence of these 2 findings in all placentas from live-born infants acquiring their infection prior to delivery indicates that they constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARS-CoV-2, and potential future studies, are discussed.


Subject(s)
COVID-19/transmission , Chorionic Villi/pathology , Infectious Disease Transmission, Vertical , Placenta Diseases/virology , Pregnancy Complications, Infectious/virology , Stillbirth , Trophoblasts/pathology , Adult , COVID-19/pathology , Chorionic Villi/virology , Chronic Disease , Female , Humans , Infant, Newborn , Male , Necrosis , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Retrospective Studies , Risk Factors , Trophoblasts/virology
18.
Viruses ; 12(11)2020 11 15.
Article in English | MEDLINE | ID: covidwho-927534

ABSTRACT

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.


Subject(s)
COVID-19/transmission , Chorionic Villi/pathology , Necrosis/pathology , Pregnancy Complications, Infectious/pathology , SARS-CoV-2/pathogenicity , Trophoblasts/pathology , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Chorionic Villi/virology , Female , Fetal Mortality , Fetus , Humans , Infectious Disease Transmission, Vertical/statistics & numerical data , Necrosis/mortality , Necrosis/virology , Pregnancy , Pregnancy Complications, Infectious/mortality , Pregnancy Complications, Infectious/virology , RNA, Viral/biosynthesis , Risk Factors , Severity of Illness Index , Survival Analysis , Trophoblasts/virology , Virus Replication
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