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1.
Front Immunol ; 13: 876555, 2022.
Article in English | MEDLINE | ID: covidwho-1809408

ABSTRACT

SARS-CoV-2 infects cells via binding to ACE2 and TMPRSS2, which allows the virus to fuse with host cells. The viral RNA is detected in the placenta of SARS-CoV-2-infected pregnant women and infection is associated with adverse pregnancy complications. Therefore, we hypothesize that SARS-CoV-2 infection of placental cells induces pro-inflammatory cytokine release to contribute to placental dysfunction and impaired pregnancy outcomes. First, expression of ACE2 and TMPRSS2 was measured by qPCR in human primary cultured term cytotrophoblasts (CTBs), syncytiotrophoblast (STBs), term and first trimester decidual cells (TDCs and FTDCs, respectively), endometrial stromal cells (HESCs) as well as trophoblast cell lines HTR8, JEG3, placental microvascular endothelial cells (PMVECs) and endometrial endothelial cells (HEECs). Later, cultured HTR8, JEG3, PMVECs and HEECs were treated with 10, 100, 1000 ng/ml of recombinant (rh-) SARS-CoV-2 S-protein ± 10 ng/ml rh-IFNγ. Pro-inflammatory cytokines IL-1ß, 6 and 8, chemokines CCL2, CCL5, CXCL9 and CXCL10 as well as tissue factor (F3), the primary initiator of the extrinsic coagulation cascade, were measured by qPCR as well as secreted IL-6 and IL-8 levels were measured by ELISA. Immunohistochemical staining for SARS-CoV-2 spike protein was performed in placental specimens from SARS-CoV-2-positive and normal pregnancies. ACE2 levels were significantly higher in CTBs and STBs vs. TDCs, FTDCs and HESCs, while TMPRSS2 levels were not detected in TDCs, FTDCs and HESCs. HTR8 and JEG3 express ACE2 and TMPRSS2, while PMVECs and HEECs express only ACE2, but not TMPRSS2. rh-S-protein increased proinflammatory cytokines and chemokines levels in both trophoblast and endothelial cells, whereas rh-S-protein only elevated F3 levels in endothelial cells. rh-IFNγ ± rh-S-protein augments expression of cytokines and chemokines in trophoblast and endothelial cells. Elevated F3 expression by rh-IFNγ ± S-protein was observed only in PMVECs. In placental specimens from SARS-CoV-2-infected mothers, endothelial cells displayed higher immunoreactivity against spike protein. These findings indicated that SARS-CoV-2 infection in placental cells: 1) induces pro-inflammatory cytokine and chemokine release, which may contribute to the cytokine storm observed in severely infected pregnant women and related placental dysfunction; and 2) elevates F3 expression that may trigger systemic or placental thrombosis.


Subject(s)
COVID-19 , Placenta Diseases , Pregnancy Complications, Infectious , Angiotensin-Converting Enzyme 2 , Cell Line, Tumor , Cytokines/metabolism , Endothelial Cells/pathology , Female , Humans , Placenta/metabolism , Placenta Diseases/pathology , Pregnancy , Pregnant Women , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Thromboplastin/metabolism
2.
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
4.
Viruses ; 13(12)2021 12 19.
Article in English | MEDLINE | ID: covidwho-1580422

ABSTRACT

BACKGROUND: SARS-CoV-2 infection in pregnant women can lead to placental damage and transplacental infection transfer, and intrauterine fetal demise is an unpredictable event. CASE STUDY: A 32-year-old patient in her 38th week of pregnancy reported loss of fetal movements. She overcame mild COVID-19 with positive PCR test 22 days before. A histology of the placenta showed deposition of intervillous fibrinoid, lympho-histiocytic infiltration, scant neutrophils, clumping of villi, and extant infarctions. Immunohistochemistry identified focal SARS-CoV-2 nucleocapsid and spike protein in the syncytiotrophoblast and isolated in situ hybridization of the virus' RNA. Low ACE2 and TMPRSS2 contrasted with strong basigin/CD147 and PDL-1 positivity in the trophoblast. An autopsy of the fetus showed no morphological abnormalities except for lung interstitial infiltrate, with prevalent CD8-positive T-lymphocytes and B-lymphocytes. Immunohistochemistry and in situ hybridization proved the presence of countless dispersed SARS-CoV-2-infected epithelial and endothelial cells in the lung tissue. The potential virus-receptor protein ACE2, TMPRSS2, and CD147 expression was too low to be detected. CONCLUSION: Over three weeks' persistence of trophoblast viral infection lead to extensive intervillous fibrinoid depositions and placental infarctions. High CD147 expression might serve as the dominant receptor for the virus, and PDL-1 could limit maternal immunity in placental tissue virus clearance. The presented case indicates that the SARS-CoV-2 infection-induced changes in the placenta lead to ischemia and consecutive demise of the fetus. The infection of the fetus was without significant impact on its death. This rare complication of pregnancy can appear independently to the severity of COVID-19's clinical course in the pregnant mother.


Subject(s)
COVID-19/complications , Placenta/pathology , Pregnancy Complications, Infectious , Stillbirth , Adult , Angiotensin-Converting Enzyme 2 , B-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/diagnosis , Endothelial Cells/pathology , Female , Fetus/pathology , Humans , Infectious Disease Transmission, Vertical , Placenta/virology , Placenta Diseases/pathology , Placenta Diseases/virology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Serine Endopeptidases , Spike Glycoprotein, Coronavirus , Trophoblasts
5.
Placenta ; 117: 47-56, 2022 01.
Article in English | MEDLINE | ID: covidwho-1474964

ABSTRACT

INTRODUCTION: Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures. METHODS: This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth. RESULTS: The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein. DISCUSSION: The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.


Subject(s)
COVID-19/complications , Placenta Diseases/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/transmission , Cohort Studies , Female , Fetal Blood/immunology , Humans , Immunity, Maternally-Acquired/immunology , Infant, Newborn , Infectious Disease Transmission, Vertical , Placenta/chemistry , Placenta/pathology , Placenta/virology , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , Premature Birth , Prospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Spike Glycoprotein, Coronavirus/analysis , Spike Glycoprotein, Coronavirus/immunology
6.
Placenta ; 115: 37-44, 2021 11.
Article in English | MEDLINE | ID: covidwho-1401783

ABSTRACT

INTRODUCTION: The reported effects of SARS-CoV-2 on pregnancy outcomes are conflicting; studies frequently overlook the placenta, which is critical for the health of the mother and infant(s). This study aimed to determine the effect of pandemic stress ± SARS CoV-2 infection on placental histopathology. METHODS: Women were recruited in Canada (n = 69); France (n = 21) or in the UK (n = 25), between March and October 2020. Historic controls (N = 20) were also included. Placenta and fetal membrane samples were collected rapidly after delivery and were fixed and stained for histopathological analysis. Maternal demographical data and obstetric outcomes were recorded. RESULTS: Over 80% of the placentas from SARS-CoV-2+ pregnancies had histopathological abnormalities: predominantly structural (71-86%) or inflammatory (9-22%), depending on geographical location. Excessive fibrin was seen in all sites, whereas deciduitis (Canada), calcifications (UK), agglutinations and chorangiosis (France) predominated in different locations. The frequency of abnormalities was significantly higher than in SARS-CoV-2 negative women (50%, p < 0.05). Demographic and obstetric data were similar in the SARS-CoV-2+ women across all sites - characterised by predominantly Black/Middle Eastern women, and women with elevated body mass index. DISCUSSION: Overall, the frequency of placental abnormalities is increased in SARS-CoV-2+ women, but the incidence of placental abnormalities is also higher in SARS-CoV-2- women that gave birth during the pandemic, which highlights the importance of appropriate control groups to ascertain the roles of pandemic stress and SARS-CoV-2 infection on the placenta and pregnancy outcomes.


Subject(s)
COVID-19 , Placenta Diseases/etiology , Pregnancy Complications, Infectious , Stress, Psychological/complications , Adolescent , Adult , COVID-19/complications , COVID-19/epidemiology , COVID-19/psychology , Canada/epidemiology , Case-Control Studies , Cohort Studies , Female , France/epidemiology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Maternal-Fetal Relations/psychology , Middle Aged , Pandemics , Placenta/pathology , Placenta/virology , Placenta Diseases/epidemiology , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/psychology , Pregnancy Outcome/epidemiology , Pregnancy Outcome/psychology , Psychological Distress , SARS-CoV-2/physiology , Stress, Psychological/etiology , Stress, Psychological/pathology , United Kingdom/epidemiology , Young Adult
7.
Placenta ; 109: 72-74, 2021 06.
Article in English | MEDLINE | ID: covidwho-1386464

ABSTRACT

Whether early SARS-CoV-2 definitively increases the risk of stillbirth is unknown, though studies have suggested possible trends of stillbirth increase during the pandemic. This study of third trimester stillbirth does not identify an increase in rates during the first wave of the pandemic period, however investigation of the placental pathology demonstrates trends towards more vascular placental abnormalities.


Subject(s)
COVID-19/epidemiology , Placenta Diseases/epidemiology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Trimester, Third , Stillbirth/epidemiology , Adult , COVID-19/complications , COVID-19/mortality , Cause of Death , Female , Fetal Death/etiology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/statistics & numerical data , Pandemics , Placenta/pathology , Placenta Diseases/etiology , Placenta Diseases/pathology , Placenta Diseases/virology , Pregnancy , Pregnancy Complications, Infectious/mortality , SARS-CoV-2/physiology , United States/epidemiology , Young Adult
8.
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
9.
Arch Pathol Lab Med ; 145(11): 1341-1349, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1337799

ABSTRACT

CONTEXT.­: Case reports and rare case series have demonstrated variable placental pathology in the setting of maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In rare small studies demonstrating infection of the placental parenchyma, histologic manifestations have included variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and syncytiotrophoblast necrosis. OBJECTIVE.­: To characterize the placental pathologic features of SARS-CoV-2-infected placentas, irrespective of fetal-maternal transmission, and to examine the frequency of C4d activation in such cases. DESIGN.­: A retrospective study of 7 placentas from mothers with active SARS-CoV-2 infection and placental infection as demonstrated by RNA in situ hybridization was conducted. RESULTS.­: There were 6 placentas from live-born neonates (5 singletons, 1 nonfused diamniotic-dichorionic twin placenta), and 1 was from a stillbirth. A total of 5 of the 8 neonates (including the stillbirth) tested negative for SARS-CoV-2, and all were negative for neonatal infection. The remaining 3 neonates were well at time of discharge. All placentas were positive for SARS-CoV-2 infection by RNA in situ hybridization and demonstrated variable degrees of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. Three cases demonstrated features of fetal vascular malperfusion. CD68 highlighted intervillous histiocytes. C4d expression was present along the villous borders in 6 of 7 cases. CONCLUSIONS.­: SARS-CoV-2 placentitis is defined by the triad of histiocytic intervillositis, perivillous fibrin deposition, and trophoblast necrosis. The features may occur in cases without confirmed transplacental transmission. The damage caused by SARS-CoV-2 placentitis is likely mediated by complement activation.


Subject(s)
COVID-19/diagnosis , Placenta Diseases/diagnosis , Placenta/pathology , Placenta/virology , Pregnancy Complications, Infectious/diagnosis , Adult , Biomarkers/metabolism , CD4-Positive T-Lymphocytes/metabolism , COVID-19/immunology , COVID-19/pathology , COVID-19/transmission , COVID-19 Testing , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Lymphocyte Activation , Male , Placenta Diseases/immunology , Placenta Diseases/pathology , Placenta Diseases/virology , Pregnancy , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , Retrospective Studies , Stillbirth
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
13.
J Clin Invest ; 131(6)2021 03 15.
Article in English | MEDLINE | ID: covidwho-1133409

ABSTRACT

The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the pathophysiology of the placenta and its impact on pregnancy outcome has not yet been fully elucidated. Here, we present a comprehensive clinical, morphological, and molecular analysis of placental tissues from pregnant women with and without SARS-CoV-2 infection. SARS-CoV-2 could be detected in half of placental tissues from SARS-CoV-2-positive women. The presence of the virus was not associated with any distinctive pathological, maternal, or neonatal outcome features. SARS-CoV-2 tissue load was low in all but one patient who exhibited severe placental damage leading to neonatal neurological manifestations. The placental transcriptional response induced by high viral load of SARS-CoV-2 showed an immunopathology phenotype similar to autopsy lung tissues from patients with severe coronavirus disease 2019. This finding contrasted with the lack of inflammatory response in placental tissues from SARS-CoV-2-positive women with low viral tissue load and from SARS-CoV-2-negative women. Importantly, no evidence of vertical transmission of SARS-CoV-2 was found in any newborns, suggesting that the placenta may be an effective maternal-neonatal barrier against the virus even in the presence of severe infection. Our observations suggest that severe placental damage induced by the virus may be detrimental for the neonate independently of vertical transmission.


Subject(s)
COVID-19/complications , COVID-19/virology , Placenta Diseases/virology , Pregnancy Complications, Infectious/virology , Adult , COVID-19/transmission , Cohort Studies , Female , Gene Expression Profiling , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Pandemics , Placenta/pathology , Placenta/virology , Placenta Diseases/genetics , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/genetics , Pregnancy Complications, Infectious/pathology , Pregnancy Outcome , RNA, Viral/genetics , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Young Adult
14.
Eur J Obstet Gynecol Reprod Biol ; 259: 7-11, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1068900

ABSTRACT

BACKGROUND: The pandemic of the severe acute respiratory distress syndrome-associated Coronavirus-2 (SARS-CoV-2) has affected millions around the world. In pregnancy the dangers to the mother and fetus are still being explored. SARS-CoV2 can potentially compromise maternal and neonatal outcomes and this may be dependent on the pregnancy stage during which the infection occurs. OBJECTIVE: The present study was done to find the histopathological alterations in the placenta of SARS-CoV-2 positive pregnancies with either no symptoms or mild coronavirus disease (COVID)-19 related symptoms and its association with neonatal outcomes. STUDY DESIGN: This was a prospective analytical study. Twenty seven asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women with a singleton pregnancy delivered between 1st July 2020 and 15th September 2020, were included as cases. An equal number of SARS-CoV-2 negative singleton pregnancies matched for maternal and gestational age during the same period were included as controls. After delivery the histopathological examination of the placenta of these women was done and the findings recorded on a predesigned proforma based on the Amsterdam consensus criteria for evidence of maternal and fetal vascular malperfusion changes. RESULTS: The baseline characteristics were comparable between the cases and controls. The following features of maternal vascular malperfusion (MVM) were significantly higher in the placentae of COVID-19 positive pregnancies: retroplacental hematomas (RPH), accelerated villous maturation (AVM), distal villous hyperplasia (DVH), atherosis, fibrinoid necrosis, mural hypertrophy of membrane arterioles (MHMA), vessel ectasia and persistence of intramural endovascular trophoblast (PIEVT). Fetal vascular malperfusion (FVM) significantly associated with the positive pregnancies were chorioangiosis, thrombosis of the fetal chorionic plate (TFCP), intramural fibrin deposition (IMFD) and vascular ectasia. Additionally, perivillous fibrin deposition was also significantly higher in the placentae of cases. The percentage of spontaneously delivered women was comparable in the two groups. The sex and weight of the newborn and the number of live births were comparable between the two groups. CONCLUSIONS: Asymptomatic or mildly symptomatic SARS-CoV-2 positive pregnant women, with otherwise uncomplicated pregnancies, show evidence of placental injury at a microscopic level. Similar findings have been demonstrated in other studies too. This placental injury apparently does not lead to poor pregnancy outcomes. The extent of this injury in symptomatic cases of COVID-19 pregnancies and its consequences on the outcomes need to be analysed.


Subject(s)
COVID-19/pathology , Placenta Diseases/pathology , Placenta/pathology , Pregnancy Complications, Infectious/pathology , Adult , Birth Weight , COVID-19/complications , COVID-19/physiopathology , Carrier State , Case-Control Studies , Female , Humans , Infant, Newborn , Male , Placenta/blood supply , Placenta Diseases/etiology , Placenta Diseases/physiopathology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2 , Severity of Illness Index , Young Adult
15.
Placenta ; 104: 261-266, 2021 01 15.
Article in English | MEDLINE | ID: covidwho-1065532

ABSTRACT

We present a case of third trimester pregnancy complicated by SARS-CoV-2 infection and subsequent reduced fetal movements, resulting in emergency Caesarean delivery with demonstrable placental SARS-CoV-2 placentitis. We show through illustration of this case and literature review that SARS-Co-V-2 placentitis is an uncommon but readily recognisable complication of maternal SARS-CoV-2 infection that may be a marker of potential vertical transmission and that may have the capacity to cause fetal compromise through a direct injurious effect on the placenta.


Subject(s)
COVID-19/complications , Placenta Diseases/virology , Placenta/pathology , Pregnancy Complications, Infectious/virology , Adult , COVID-19/pathology , Female , Humans , Placenta Diseases/pathology , Pregnancy , Pregnancy Complications, Infectious/pathology , Pregnancy Trimester, Third , SARS-CoV-2
16.
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
17.
Am J Obstet Gynecol ; 224(4): 382.e1-382.e18, 2021 04.
Article in English | MEDLINE | ID: covidwho-956872

ABSTRACT

BACKGROUND: There is a paucity of data describing the effects of coronavirus disease 2019 on placental pathology, especially in asymptomatic patients. Although the pathophysiology of coronavirus disease 2019 is not completely understood, there is emerging evidence that it causes a severe systemic inflammatory response and results in a hypercoagulable state with widespread microthrombi. We hypothesized that it is plausible that a similar disease process may occur in the fetal-maternal unit. OBJECTIVE: This study aimed to determine whether coronavirus disease 2019 in term patients admitted to labor and delivery, including women without coronavirus disease 2019 symptomatology, is associated with increased placental injury compared with a cohort of coronavirus disease 2019-negative controls. STUDY DESIGN: This was a retrospective cohort study performed at NYU Winthrop Hospital between March 31, 2020, and June 17, 2020. During the study period, all women admitted to labor and delivery were routinely tested for severe acute respiratory syndrome coronavirus 2 regardless of symptomatology. The placental histopathologic findings of patients with coronavirus disease 2019 (n=77) who delivered a singleton gestation at term were compared with a control group of term patients without coronavirus disease 2019 (n=56). Controls were excluded if they had obstetrical or medical complications including fetal growth restriction, oligohydramnios, hypertension, diabetes, coagulopathy, or thrombophilia. Multivariable logistic regression models were performed for variables that were significant (P<.05) in univariable analyses. A subgroup analysis was also performed comparing asymptomatic coronavirus disease 2019 cases with negative controls. RESULTS: In univariable analyses, coronavirus disease 2019 cases were more likely to have evidence of fetal vascular malperfusion, that is, presence of avascular villi and mural fibrin deposition (32.5% [25/77] vs 3.6% [2/56], P<.0001) and villitis of unknown etiology (20.8% [16/77] vs 7.1% [4/56], P=.030). These findings persisted in a subgroup analysis of asymptomatic coronavirus disease 2019 cases compared with coronavirus disease 2019-negative controls. In a multivariable model adjusting for maternal age, race and ethnicity, mode of delivery, preeclampsia, fetal growth restriction, and oligohydramnios, the frequency of fetal vascular malperfusion abnormalities remained significantly higher in the coronavirus disease 2019 group (odds ratio, 12.63; 95% confidence interval, 2.40-66.40). Although the frequency of villitis of unknown etiology was more than double in coronavirus disease 2019 cases compared with controls, this did not reach statistical significance in a similar multivariable model (odds ratio, 2.11; 95% confidence interval, 0.50-8.97). All neonates of mothers with coronavirus disease 2019 tested negative for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction. CONCLUSION: Despite the fact that all neonates born to mothers with coronavirus disease 2019 were negative for severe acute respiratory syndrome coronavirus 2 by polymerase chain reaction, we found that coronavirus disease 2019 in term patients admitted to labor and delivery is associated with increased rates of placental histopathologic abnormalities, particularly fetal vascular malperfusion and villitis of unknown etiology. These findings seem to occur even among asymptomatic term patients.


Subject(s)
COVID-19/pathology , Placenta/pathology , Pregnancy Complications, Infectious/pathology , SARS-CoV-2 , Adult , Female , Fetus/blood supply , Humans , Infant, Newborn , Logistic Models , Placenta Diseases/pathology , Pregnancy , Retrospective Studies
19.
Am J Physiol Endocrinol Metab ; 319(2): E315-E319, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-612219

ABSTRACT

The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to maternal and newborn health has yet to be determined. Several reports suggest pregnancy does not typically increase the severity of maternal disease; however, cases of preeclampsia and preterm birth have been infrequently reported. Reports of placental infection and vertical transmission are rare. Interestingly, despite lack of SARS-CoV-2 placenta infection, there are several reports of significant abnormalities in placenta morphology. Continued research on pregnant women infected with SARS-CoV-2 and their offspring is vitally important.


Subject(s)
Coronavirus Infections/physiopathology , Infectious Disease Transmission, Vertical , Placenta Diseases/physiopathology , Pneumonia, Viral/physiopathology , Pregnancy Complications, Infectious/physiopathology , Abortion, Spontaneous , Betacoronavirus , COVID-19 , Cesarean Section , Coronavirus Infections/complications , Coronavirus Infections/transmission , Delivery, Obstetric , Female , Fetal Death , Gestational Age , Humans , Infant, Newborn , Pandemics , Placenta Diseases/etiology , Placenta Diseases/pathology , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Pregnancy , Premature Birth , SARS-CoV-2 , Severity of Illness Index
20.
Pediatr Dev Pathol ; 23(3): 177-180, 2020.
Article in English | MEDLINE | ID: covidwho-244953

ABSTRACT

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.


Subject(s)
Coronavirus Infections/complications , Coronavirus Infections/pathology , Placenta Diseases/etiology , Placenta Diseases/pathology , Placenta/pathology , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Pregnancy Complications, Infectious/pathology , Thrombosis/etiology , Adolescent , Adult , COVID-19 , Female , Fetal Diseases/etiology , Fetal Diseases/pathology , Humans , Infant, Newborn , New York , Pandemics , Pregnancy , Thrombosis/pathology , Young Adult
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