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1.
Viruses ; 13(12)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1572671

ABSTRACT

Neonatal COVID-19 is rare and mainly results from postnatal transmission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, can infect the placenta and compromise its function. We present two cases of decreased fetal movements and abnormal fetal heart rhythm 5 days after mild maternal COVID-19, requiring emergency caesarean section at 29 + 3 and 32 + 1 weeks of gestation, and leading to brain injury. Placental examination revealed extensive and multifocal chronic intervillositis, with intense cytoplasmic positivity for SARS-CoV-2 spike antibody and SARS-CoV-2 detection by RT-qPCR. Vertical transmission was confirmed in one case, and both neonates developed extensive cystic peri-ventricular leukomalacia.


Subject(s)
Brain Injuries/etiology , COVID-19/complications , Placenta/virology , Pregnancy Complications, Infectious/virology , Adult , Brain Injuries/pathology , COVID-19/physiopathology , COVID-19/virology , Cesarean Section , Female , Fetal Movement , Humans , Infant, Newborn , Infant, Premature , Infectious Disease Transmission, Vertical , Leukomalacia, Periventricular/etiology , Leukomalacia, Periventricular/pathology , Placenta/pathology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , SARS-CoV-2/isolation & purification
2.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1511731

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Placenta/pathology , Pregnancy Complications, Infectious/therapy , Adult , COVID-19/diagnosis , Cesarean Section , Female , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Trimester, Second , Treatment Outcome
3.
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
4.
Front Immunol ; 12: 743022, 2021.
Article in English | MEDLINE | ID: covidwho-1450814

ABSTRACT

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. The virus primarily affects the lungs where it induces respiratory distress syndrome ranging from mild to acute, however, there is a growing body of evidence supporting its negative effects on other system organs that also carry the ACE2 receptor, such as the placenta. The majority of newborns delivered from SARS-CoV-2 positive mothers test negative following delivery, suggesting that there are protective mechanisms within the placenta. There appears to be a higher incidence of pregnancy-related complications in SARS-CoV-2 positive mothers, such as miscarriage, restricted fetal growth, or still-birth. In this review, we discuss the pathobiology of COVID-19 maternal infection and the potential adverse effects associated with viral infection, and the possibility of transplacental transmission.


Subject(s)
COVID-19/pathology , Placenta/pathology , Placenta/virology , Pregnancy Complications, Infectious/virology , Abortion, Spontaneous/virology , Angiotensin-Converting Enzyme 2/metabolism , Female , Fetal Growth Retardation/virology , Humans , Maternal-Fetal Exchange/physiology , Pregnancy , SARS-CoV-2/pathogenicity , Serine Endopeptidases/metabolism , Stillbirth
5.
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
7.
Viruses ; 13(9)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1430983

ABSTRACT

(1) This study aimed to evaluate characteristics, perinatal outcomes, and placental pathology of pregnant women with or without SARS-CoV-2 infection in the context of maternal PCR cycle threshold (CT) values. (2) This was a retrospective case-control study in a third-level health center in Mexico City with universal screening by RT-qPCR. The association of COVID-19 manifestations, preeclampsia, and preterm birth with maternal variables and CT values were assessed by logistic regression models and decision trees. (3) Accordingly, 828 and 298 women had a negative and positive test, respectively. Of those positive, only 2.6% of them presented mild to moderate symptoms. Clinical characteristics between both groups of women were similar. No associations between CT values were found for maternal features, such as pre-gestational BMI, age, and symptomatology. A significantly higher percentage of placental fibrinoid was seen with women with low CTs (<25; p < 0.01). Regarding perinatal outcomes, preeclampsia was found to be significantly associated with symptomatology but not with risk factors or CT values (p < 0.01, aOR = 14.72). Moreover, 88.9% of women diagnosed with COVID-19 at <35 gestational weeks and symptomatic developed preeclampsia. (4) The data support strong guidance for pregnancies with SARS-CoV-2 infection, in particular preeclampsia and placental pathology, which need further investigation.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/physiology , Adult , Biopsy , COVID-19/diagnosis , Female , Humans , Immunohistochemistry , Infectious Disease Transmission, Vertical , Placenta/pathology , Placenta/virology , Polymerase Chain Reaction , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome , Retrospective Studies , Young Adult
8.
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
9.
Int J Mol Sci ; 22(6)2021 Mar 13.
Article in English | MEDLINE | ID: covidwho-1389393

ABSTRACT

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.


Subject(s)
Immunity , Placenta/immunology , Placenta/virology , Pregnancy Complications, Infectious/immunology , Pregnancy Complications, Infectious/virology , Virus Diseases/immunology , Viruses/immunology , Female , Fetus/immunology , Fetus/virology , Humans , Placenta/pathology , Pregnancy , Trophoblasts/immunology , Trophoblasts/virology
10.
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
11.
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
12.
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
13.
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
15.
Am J Surg Pathol ; 46(1): 51-57, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1324832

ABSTRACT

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at different points in the pregnancy timeline may affect maternal and fetal outcomes remains unknown. We sought to characterize the impact of SARS-CoV-2 infection proximate and remote from delivery on placental pathology. We performed a secondary analysis of placental pathology from a prospective cohort of universally tested SARS-CoV-2 positive women >20 weeks gestation at 1 institution. Subjects were categorized as having acute or nonacute SARS-CoV-2 based on infection <14 or ≥14 days from delivery admission, respectively, determined by nasopharyngeal swab, symptom history, and serologies, when available. A subset of SARS-CoV-2 negative women represented negative controls. Placental pathology was available for 90/97 (92.8%) of SARS-CoV-2 positive women, of which 26 were from women with acute SARS-CoV-2 infection and 64 were from women with nonacute SARS-CoV-2. Fetal vascular malperfusion lesions were significantly more frequent among the acute SARS-CoV-2 group compared with the nonacute SARS-CoV-2 group (53.8% vs. 18.8%; P=0.002), while frequency of maternal vascular malperfusion lesions did not differ by timing of infection (30.8% vs. 29.7%; P>0.99). When including 188 SARS-CoV-2 negative placentas, significant differences in frequency of fetal vascular malperfusion lesions remained between acute, nonacute and control cases (53.8% vs. 18.8% vs. 13.2%, respectively; P<0.001). No differences were noted in obstetric or neonatal outcomes between acutely and nonacutely infected women. Our findings indicate timing of infection in relation to delivery may alter placental pathology, with potential clinical implications for risk of thromboembolic events and impact on fetal health.


Subject(s)
COVID-19/pathology , Placenta/blood supply , Placenta/pathology , Pregnancy Complications, Infectious/pathology , Adult , Case-Control Studies , Female , Gestational Age , Humans , Ischemia/pathology , Ischemia/virology , Patient Acuity , Placenta/virology , Pregnancy , Prospective Studies
16.
Front Immunol ; 12: 685919, 2021.
Article in English | MEDLINE | ID: covidwho-1268252

ABSTRACT

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described. Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group). Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker. Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis. Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.


Subject(s)
COVID-19/pathology , COVID-19/virology , Placenta/pathology , Pregnancy Complications, Infectious/pathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/physiology , Adult , Brazil , COVID-19/immunology , COVID-19/transmission , Case-Control Studies , Female , Gestational Age , Host-Pathogen Interactions/immunology , Humans , Immunohistochemistry , Infectious Disease Transmission, Vertical , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/immunology , RNA, Viral , Viral Load
17.
Pediatr Dev Pathol ; 24(5): 450-454, 2021.
Article in English | MEDLINE | ID: covidwho-1259128

ABSTRACT

An emerging complication of COVID-19 (SARS-CoV-2) infection is reported. A 23-year-old patient presented with high temperature and reduced fetal movements at 25 + 5/40 weeks of gestation. RT-PCR proved maternal COVID-19 infection. Ultrasound examination confirmed intrauterine death. Placenta histology showed necrosis of the villous trophoblast, associated with Chronic Histiocytic Intervillositis (CHI) and Massive Perivillous Fibrin Deposition (MPFD) with up to 90% - of the intervillous spaces being involved. Immunohistochemistry showed CD68 positive histiocytes in the intervillous spaces and the villous trophoblast was positive for the COVID-19 spike protein. RNA scope signal was indicative of the presence of the viral genome and active viral replication in the villous trophoblastic cells, respectively. MPFD is a gradually developing end-stage disease with various etiology, including autoimmune and alloimmune maternal response to antigens expressed at the feto-maternal interface and frequently accompanies chronic alloimmune villitis or histiocytic intervillositis. Covid-19 infection is associated with similar pattern of histological changes of the placenta leading to placental insufficiency and fetal death. This case report supports maternal- fetal vertical transmission of SARS-CoV-2 virus leading to placental insufficiency and fetal demise. MPFD and CHI appear to be the typical placental histology for SARS-CoV-2 virus infection associated fetal demise.


Subject(s)
COVID-19/virology , Chorionic Villi/virology , Fibrin/metabolism , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Adult , Chorionic Villi/pathology , Female , Fetal Death/etiology , Histiocytes/virology , Humans , Placenta/pathology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/pathology , RNA, Viral
18.
Int J Mol Sci ; 22(11)2021 May 28.
Article in English | MEDLINE | ID: covidwho-1256562

ABSTRACT

A pandemic of acute respiratory infections, due to a new type of coronavirus, can cause Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) and has created the need for a better understanding of the clinical, epidemiological, and pathological features of COVID-19, especially in high-risk groups, such as pregnant women. Viral infections in pregnant women may have a much more severe course, and result in an increase in the rate of complications, including spontaneous abortion, stillbirth, and premature birth-which may cause long-term consequences in the offspring. In this review, we focus on the mother-fetal-placenta interface and its role in the potential transmission of SARS-CoV-2, including expression of viral receptors and proteases, placental pathology, and the presence of the virus in neonatal tissues and fluids. This review summarizes the current knowledge on the anti-viral activity of lactoferrin during viral infection in pregnant women, analyzes its role in the pathogenicity of pandemic virus particles, and describes the potential evidence for placental blocking/limiting of the transmission of the virus.


Subject(s)
Anti-Infective Agents/pharmacology , COVID-19/immunology , Infectious Disease Transmission, Vertical/prevention & control , Lactoferrin/pharmacology , Placenta/immunology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/immunology , COVID-19/complications , Female , Humans , Infant, Newborn , Lactoferrin/metabolism , Placenta/pathology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/immunology
19.
Rev Bras Ginecol Obstet ; 43(6): 474-479, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1254108

ABSTRACT

Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on the maternal/neonatal outcomes. This brief review provides an overview about some aspects of the placental pathology in SARS-CoV-2 infection. In total, 11 papers were included. The current literature suggests that there are no specific histopathological characteristics in the placenta related to SARS-CoV-2 infection, but placentas from infected women are more likely to show findings of maternal and/or fetal malperfusion. The most common findings in placentas from infected women were fibrin deposition and intense recruitment of inflammatory infiltrates. The transplacental transmission of this virus is unlikely to occur, probably due to low expression of the receptor for SARS-CoV-2 in placental cell types. Further studies are needed to improve our knowledge about the interaction between the virus and the mother-fetus dyad and the impact on maternal and neonatal/fetal outcomes.


Subject(s)
COVID-19/pathology , Placenta/pathology , Pregnancy Complications, Infectious/pathology , COVID-19/physiopathology , COVID-19/virology , Female , Humans , Infectious Disease Transmission, Vertical , Placenta/blood supply , Placenta/physiopathology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/virology
20.
Viruses ; 13(6)2021 05 26.
Article in English | MEDLINE | ID: covidwho-1244151

ABSTRACT

The current coronavirus pandemic has affected, in a short time, various and different areas of medicine. Among these, the obstetric field has certainly been touched in full, and the knowledge of the mechanisms potentially responsible for placental damage from SARS-CoV-2 occupy a certain importance. Here we present here a rare case of dichorionic twins born at 30 weeks and 4 days of amenorrhea, one of whom died in the first few hours of life after placental damages potentially related to SARS-CoV-2. We also propose a brief review of the current literature giving ample emphasis to similar cases described.


Subject(s)
COVID-19/complications , Placenta/pathology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/pathogenicity , Adult , COVID-19/diagnosis , COVID-19/transmission , COVID-19/virology , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Obstetric Labor Complications/virology , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Outcome , Pregnancy, Twin , SARS-CoV-2/isolation & purification
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