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1.
Mod Pathol ; 35(9): 1175-1180, 2022 09.
Article in English | MEDLINE | ID: covidwho-2016645

ABSTRACT

Current public health initiatives to contain the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic focus on expanding vaccination efforts to include vulnerable populations such as pregnant people. Vaccines using messenger ribonucleic acid (mRNA) technology rely on translation by immune cells, primarily at the injection site. Hesitancy remains among the general population regarding the safety of mRNA vaccines during gestation, and it remains unknown whether the SARS-CoV-2 Spike protein (the product of mRNA vaccines available) accumulates in the placenta after vaccination. Objective: To determine whether Spike protein translation and accumulation occurs in placental tissue in the context of recent mRNA SARC-CoV-2 vaccination during pregnancy. We identified 48 patients receiving one or two doses of mRNA SARS-CoV-2 vaccine during gestation and used immunohistochemistry against SARS-CoV-2 Spike protein in formalin-fixed, paraffin-embedded placental tissue. One placenta, positive for SARS-CoV-2 RNA by in situ hybridization (ISH) was used as positive control. Seven term placentas collected prior to the emergence of SARS-CoV-2 served as negative controls. Eighty one percent of patients in the study group underwent third-trimester delivery; remaining had a first-trimester spontaneous abortion or elective second-trimester termination. Patients received two (52%) or one (48%) vaccine doses during pregnancy, with a median interval between latest dose and delivery of 13 days (range 2-79 days). Most (63%) cases had their latest dose within 15 days prior to delivery. All the placentas in the study and negative control groups were negative for SARS-CoV-2 immunohistochemistry. Six study cases with short vaccine-delivery intervals (2-7 days) were subjected to SARS-CoV-2 ISH and were negative. Our findings suggest that mRNA vaccines do not reach significant concentrations in the placenta given the absence of definitive SARS-CoV-2 Spike protein accumulation in placental tissue. This observation provides evidence supporting the safety of mRNA vaccines to the placental-fetal unit.


Subject(s)
COVID-19 Vaccines , COVID-19 , Placenta , Pregnancy Complications, Infectious , Spike Glycoprotein, Coronavirus , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Female , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/analysis , Vaccination
2.
BMC Pregnancy Childbirth ; 21(1): 760, 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1923523

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.
Int J Mol Sci ; 23(4)2022 Feb 14.
Article in English | MEDLINE | ID: covidwho-1686821

ABSTRACT

The ongoing COVID-19 pandemic dictated new priorities in biomedicine research. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is a single-stranded positive-sense RNA virus. In this pilot study, we optimized our padlock assay to visualize genomic and subgenomic regions using formalin-fixed paraffin-embedded placental samples obtained from a confirmed case of COVID-19. SARS-CoV-2 RNA was localized in trophoblastic cells. We also checked the presence of the virion by immunolocalization of its glycoprotein spike. In addition, we imaged mitochondria of placental villi keeping in mind that the mitochondrion has been suggested as a potential residence of the SARS-CoV-2 genome. We observed a substantial overlapping of SARS-CoV-2 RNA and mitochondria in trophoblastic cells. This intriguing linkage correlated with an aberrant mitochondrial network. Overall, to the best of our knowledge, this is the first study that provides evidence of colocalization of the SARS-CoV-2 genome and mitochondria in SARS-CoV-2 infected tissue. These findings also support the notion that SARS-CoV-2 infection can reprogram mitochondrial activity in the highly specialized maternal-fetal interface.


Subject(s)
Mitochondria/virology , Nucleic Acid Amplification Techniques/methods , Placenta/virology , RNA, Viral/metabolism , SARS-CoV-2/genetics , Adult , COVID-19/pathology , COVID-19/virology , DNA Probes/metabolism , Female , Humans , Pilot Projects , Placenta/pathology , Pregnancy , SARS-CoV-2/isolation & purification
4.
Pediatr Res ; 91(2): 432-439, 2022 01.
Article in English | MEDLINE | ID: covidwho-1671538

ABSTRACT

The SARS-CoV-2 pandemic has had a significant impact worldwide, particularly in middle- and low-income countries. While this impact has been well-recognized in certain age groups, the effects, both direct and indirect, on the neonatal population remain largely unknown. There are placental changes associated, though the contributions to maternal and fetal illness have not been fully determined. The rate of premature delivery has increased and SARS-CoV-2 infection is proportionately higher in premature neonates, which appears to be related to premature delivery for maternal reasons rather than an increase in spontaneous preterm labor. There is much room for expansion, including long-term data on outcomes for affected babies. Though uncommon, there has been evidence of adverse events in neonates, including Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C). There are recommendations for reduction of viral transmission to neonates, though more research is required to determine the role of passive immunization of the fetus via maternal vaccination. There is now considerable evidence suggesting that the severe visitation restrictions implemented early in the pandemic have negatively impacted the care of the neonate and the experiences of both parents and healthcare professionals alike. Ongoing collaboration is required to determine the full impact, and guidelines for future management. IMPACT: Comprehensive review of current available evidence related to impact of the COVID-19 pandemic on neonates, effects on their health, impact on their quality of care and indirect influences on their clinical course, including comparisons with other age groups. Reference to current evidence for maternal experience of infection and how it impacts the fetus and then neonate. Outline of the need for ongoing research, including specific areas in which there are significant gaps in knowledge.


Subject(s)
COVID-19/complications , Infant, Newborn, Diseases , COVID-19/prevention & control , COVID-19/virology , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Maternal-Fetal Exchange , Placenta/virology , Pregnancy , Premature Birth , SARS-CoV-2/isolation & purification , Systemic Inflammatory Response Syndrome/complications
5.
Nat Commun ; 13(1): 320, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1632529

ABSTRACT

Pregnant women represent a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Here we show that SARS-CoV-2 infection during pregnancy primarily induces unique inflammatory responses at the maternal-fetal interface, which are largely governed by maternal T cells and fetal stromal cells. SARS-CoV-2 infection during pregnancy is also associated with humoral and cellular immune responses in the maternal blood, as well as with a mild cytokine response in the neonatal circulation (i.e., umbilical cord blood), without compromising the T-cell repertoire or initiating IgM responses. Importantly, SARS-CoV-2 is not detected in the placental tissues, nor is the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and emphasizes the rarity of placental infection.


Subject(s)
COVID-19/immunology , Immunity/immunology , Infectious Disease Transmission, Vertical , Placenta/immunology , Pregnancy Complications, Infectious/immunology , SARS-CoV-2/immunology , Adult , COVID-19/blood , COVID-19/virology , Cytokines/blood , Cytokines/immunology , Cytokines/metabolism , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Infant, Newborn , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/virology , RNA, Viral/genetics , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Young Adult
6.
J Infect Dis ; 225(5): 754-758, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1621621

ABSTRACT

There is limited information on the specific impact of maternal infection with the SARS-CoV-2 B.1.617.2 (delta) variant on pregnancy outcomes. We present 2 cases of intrauterine fetal demise and 1 case of severe fetal distress in the setting of maternal infection with delta-variant SARS-CoV-2. In all cases, fetal demise or distress occurred within 14 days of COVID-19 diagnosis. Evaluation revealed maternal viremia, high nasopharyngeal viral load, evidence of placental infection with delta-variant SARS-CoV-2, and hallmark features of SARS-CoV-2 placentitis. We suggest that delta-variant SARS-CoV-2 infection during pregnancy warrants vigilance for placental dysfunction and fetal compromise regardless of disease severity.


Subject(s)
COVID-19/diagnosis , Fetal Death , Fetal Distress , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2 , Adult , COVID-19/complications , COVID-19/mortality , COVID-19 Testing , Chorioamnionitis , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnancy Complications, Infectious/diagnosis
7.
J Infect Dis ; 225(5): 748-753, 2022 03 02.
Article in English | MEDLINE | ID: covidwho-1621620

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a higher infection rate in pregnant women than age-matched adults. With increased infectivity and transmissibility, the Delta variant is predominant worldwide. METHODS: In this study, we describe intrauterine fetal demise in unvaccinated women with mild symptoms of SARS-CoV-2 Delta variant infection. RESULTS: Histology and elevated proinflammatory responses of the placenta suggest that fetal demise was associated with placental malperfusion due to Delta variant infection. CONCLUSIONS: This study suggests that the Delta variant can cause severe morbidity and mortality to fetuses. Vaccination should continue to be advocated and will likely continue to reduce SARS-CoV-2 infection risks for pregnant women and their fetuses.


Subject(s)
COVID-19/diagnosis , Fetal Death , Pregnancy Complications, Infectious/virology , SARS-CoV-2/isolation & purification , Stillbirth , Adult , Female , Fetal Death/etiology , Humans , Infectious Disease Transmission, Vertical , Placenta/virology , Pregnancy , Pregnancy Trimester, Third
8.
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
9.
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
10.
J Med Virol ; 93(12): 6788-6793, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1562395

ABSTRACT

This study aimed to report a case of mild novel coronavirus disease (COVID-19) in a pregnant woman with probable viremia, as reverse transcription-polymerase chain reaction (RT-PCR) testing of endometrial and placental swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. A 26-year-old multigravida at 35 weeks 2 days of gestation, who had extensive thigh and abdominal cellulitis, tested SARS-CoV-2 positive by RT-PCR performed on samples from the endometrium and maternal side of the placenta. However, other samples (amniotic fluid, fetal side of the placenta, umbilical cord, maternal vagina, and neonatal nasopharynx) tested negative for SARS-CoV-2. This is one of the rare reports of probable SARS-CoV-2 viremia with the presence of SARS-CoV-2 in the endometrium and placenta, but not leading to vertical transmission and neonatal infection. Because knowledge about transplacental transmission and results is very limited, we conclude that more RT-PCR tests on placental and cord blood samples are needed in order to safely make definite conclusions.


Subject(s)
COVID-19/virology , Fetus/virology , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/genetics , Viremia/virology , Adult , Female , Humans , Infectious Disease Transmission, Vertical , Pregnancy , Pregnant Women
11.
J Infect Dis ; 224(Supplement_6): S642-S646, 2021 Dec 08.
Article in English | MEDLINE | ID: covidwho-1559852

ABSTRACT

We previously demonstrated that the late gestation placental expression pattern of ACE2 (the primary severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] receptor) is localized to the villous syncytiotrophoblast (ST), usually in a polarized membranous pattern at the ST base sparing the apical surface (that directly exposed to maternal blood). We found that the late gestation placental expression pattern of TMPRSS2 (the spike proteinase required for SARS-CoV-2 cellular infection), is usually absent in the trophoblast but is rarely, weakly expressed in the placental endothelium. We now show the developmental protein expression patterns of ACE2 and TMPRSS2 by immunohistochemistry throughout gestation, from the first through third trimester. We found that TMPRSS2 expression was rarely detectable in villous endothelium and very rarely detectable in the ST across gestation. We found that ACE2 expression varied during gestation with circumferential ST expression more common in early gestations and polarized expression more common in later gestation. Although this study is small, these preliminary results suggest that earlier gestation pregnancies may be more vulnerable to infection than later gestation pregnancies.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Placenta/metabolism , Pregnancy Complications, Infectious/virology , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Adult , Angiotensin-Converting Enzyme 2/genetics , Female , Gestational Age , Humans , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Complications, Infectious/pathology , Serine Endopeptidases/genetics , Trophoblasts
12.
Placenta ; 117: 187-193, 2022 01.
Article in English | MEDLINE | ID: covidwho-1550030

ABSTRACT

INTRODUCTION: Recent evidence supports the - rare - occurrence of vertical transplacental SARS-CoV-2 transmission. We previously determined that placental expression of angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor, and associated viral cell entry regulators is upregulated by hypoxia. In the present study, we utilized a clinically relevant model of SARS-CoV-2-associated chronic histiocytic intervillositis/massive perivillous fibrin deposition (CHIV/MPFVD) to test the hypothesis that placental hypoxia may facilitate placental SARS-CoV-2 infection. METHODS: We performed a comparative immunohistochemical and/or RNAscope in-situ hybridization analysis of carbonic anhydrase IX (CAIX, hypoxia marker), ACE2 and SARS-CoV-2 expression in free-floating versus fibrin-encased chorionic villi in a 20-weeks' gestation placenta with SARS-CoV-2-associated CHIV/MPVFD. RESULTS: The levels of CAIX and ACE2 immunoreactivity were significantly higher in trophoblastic cells of fibrin-encased villi than in those of free-floating villi, consistent with hypoxia-induced ACE2 upregulation. SARS-CoV-2 showed a similar preferential localization to trophoblastic cells of fibrin-encased villi. DISCUSSION: The localization of SARS-CoV-2 to hypoxic, fibrin-encased villi in this placenta with CHIV/MPVFD suggests placental infection and, therefore, transplacental SARS-CoV-2 transmission may be promoted by hypoxic conditions, mediated by ACE2 and similar hypoxia-sensitive viral cell entry mechanisms. Understanding of a causative link between placental hypoxia and SARS-CoV-2 transmittability may potentially lead to the development of alternative strategies for prevention of intrauterine COVID-19 transmission.


Subject(s)
COVID-19/complications , Fibrin/analysis , Hypoxia/virology , Placenta/virology , Pregnancy Complications, Infectious/virology , SARS-CoV-2/isolation & purification , Adult , Angiotensin-Converting Enzyme 2/analysis , COVID-19/pathology , COVID-19/virology , Carbonic Anhydrase IX/analysis , Chorionic Villi/enzymology , Chorionic Villi/virology , Female , Gestational Age , Histiocytes/pathology , Humans , Hypoxia/pathology , Infectious Disease Transmission, Vertical , Necrosis/virology , Placenta/chemistry , Placenta/pathology , Pregnancy , Stillbirth , Trophoblasts/enzymology , Trophoblasts/virology
13.
Cell Rep Med ; 2(12): 100456, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1500334

ABSTRACT

The ongoing SARS-CoV-2 pandemic continues to lead to high morbidity and mortality. During pregnancy, severe maternal and neonatal outcomes and placental pathological changes have been described. We evaluate SARS-CoV-2 infection at the maternal-fetal interface using precision-cut slices (PCSs) of human placenta. Remarkably, exposure of placenta PCSs to SARS-CoV-2 leads to a full replication cycle with infectious virus release. Moreover, the susceptibility of placental tissue to SARS-CoV-2 replication relates to the expression levels of ACE2. Viral proteins and/or viral RNA are detected in syncytiotrophoblasts, cytotrophoblasts, villous stroma, and possibly Hofbauer cells. While SARS-CoV-2 infection of placenta PCSs does not cause a detectable cytotoxicity or a pro-inflammatory cytokine response, an upregulation of one order of magnitude of interferon type III transcripts is measured. In conclusion, our data demonstrate the capacity of SARS-CoV-2 to infect and propagate in human placenta and constitute a basis for further investigation of SARS-CoV-2 biology at the maternal-fetal interface.


Subject(s)
Placenta/virology , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/transmission , COVID-19/virology , Chorionic Villi/virology , Female , Humans , Infectious Disease Transmission, Vertical , Interferons/metabolism , Placenta/cytology , Placenta/metabolism , Pregnancy , RNA, Viral/metabolism , Trophoblasts/cytology , Trophoblasts/virology , Viral Proteins/metabolism , Virus Release , Virus Replication
14.
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
15.
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
16.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166285, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1460712

ABSTRACT

During pregnancy, a series of physiological changes are determined at the molecular, cellular and macroscopic level that make the mother and fetus more susceptible to certain viral and bacterial infections, especially the infections in this and the companion review. Particular situations increase susceptibility to infection in neonates. The enhanced susceptibility to certain infections increases the risk of developing particular diseases that can progress to become morbidly severe. For example, during the current pandemic caused by the SARS-CoV-2 virus, epidemiological studies have established that pregnant women with COVID-19 disease are more likely to be hospitalized. However, the risk for intensive care unit admission and mechanical ventilation is not increased compared with nonpregnant women. Although much remains unknown with this particular infection, the elevated risk of progression during pregnancy towards more severe manifestations of COVID-19 disease is not associated with an increased risk of death. In addition, the epidemiological data available in neonates suggest that their risk of acquiring COVID-19 is low compared with infants (<12 months of age). However, they might be at higher risk for progression to severe COVID-19 disease compared with older children. The data on clinical presentation and disease severity among neonates are limited and based on case reports and small case series. It is well documented the importance of the Zika virus infection as the main cause of several congenital anomalies and birth defects such as microcephaly, and also adverse pregnancy outcomes. Mycoplasma infections also increase adverse pregnancy outcomes. This review will focus on the molecular, pathophysiological and biophysical characteristics of the mother/placental-fetal/neonatal interactions and the possible mechanisms of these pathogens (SARS-CoV-2, ZIKV, and Mycoplasmas) for promoting disease at this level.


Subject(s)
COVID-19/etiology , COVID-19/transmission , Mycoplasma Infections/etiology , Mycoplasma Infections/transmission , Pregnancy Complications, Infectious , Zika Virus Infection/etiology , Zika Virus Infection/transmission , Biomarkers , Breast Feeding/adverse effects , Disease Susceptibility , Female , Host-Pathogen Interactions/immunology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Maternal-Fetal Exchange , Mycoplasma , Placenta/immunology , Placenta/metabolism , Placenta/microbiology , Placenta/virology , Pregnancy , SARS-CoV-2 , Zika Virus
17.
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
18.
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
20.
J Med Virol ; 93(10): 5864-5872, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1432419

ABSTRACT

The aim was to investigate the association of the delivery mode and vertical transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) through the samples of vaginal secretions, placenta, cord blood, or amniotic fluid as well as the neonatal outcomes. This cross-sectional study presents an analysis of prospectively gathered data collected at a single tertiary hospital. Sixty-three pregnant women with confirmed coronavirus disease 2019 (COVID-19) participated in the study. Vertical transmission of SARS-CoV-2 was analyzed with reverse transcriptase-polymerase chain reaction (RT-PCR) tests and blood tests for immunoglobulin G (IgG)-immunoglobulin M (IgM) antibodies. All patients were in the mild or moderate category for COVID-19. Only one placental sample and two of the vaginal secretion samples were positive for SARS-CoV-2. Except for one, all positive samples were obtained from patients who gave birth by cesarean. All cord blood and amniotic fluid samples were negative for SARS-CoV-2. Two newborns were screened positive for COVID-19 IgG-IgM within 24 h after delivery, but the RT-PCR tests were negative. A positive RT-PCR result was detected in a neof a mother whose placenta, cord blood, amniotic fluid, and vaginal secretions samples were negative. He died due to pulmonary hemorrhage on the 11th day of life. In conclusion, we demonstrated that SARS-CoV-2 can be detectable in the placenta or vaginal secretions of pregnant women. Detection of the virus in the placenta or vaginal secretions may not be associated with neonatal infection. Vaginal delivery may not increase the incidence of neonatal infection, and cesarean may not prevent vertical transmission. The decision regarding the mode of delivery should be based on obstetric indications and COVID-19 severity.


Subject(s)
COVID-19/transmission , SARS-CoV-2/isolation & purification , Adolescent , Adult , COVID-19/diagnosis , COVID-19/epidemiology , Cesarean Section , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/epidemiology , Infant, Newborn, Diseases/virology , Infectious Disease Transmission, Vertical/statistics & numerical data , Male , Placenta/virology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Pregnancy Outcome , Prospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Tertiary Care Centers , Vagina/virology , Young Adult
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