Transplacental Transmission of COVID-19

Study Overview
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Brief Summary
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SARS-CoV-2, the agent responsible for pandemic COVID-19 infection, is transmitted mainly by respiratory droplets. Regarding maternal-fetal transmission, even if the mode of transmission from mother to fetus is not clear, some cases of perinatal transmission have been described, but without certainty on the routes of placental contamination, trans-cervical or by environmental exposure. . The case described by J. Vivanti of a newborn with neonatal neurological involvement and whose mother had been infected during the last trimester of pregnancy reports possible transplacental transmission in a context of positive and elevated viremia in the mother and positive viremia in the newborn.

Detailed Description
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In 2021, it becomes essential to clarify if and how SARS-COV-2 reaches the fetus, in order to prevent neonatal infection, optimize pregnancy management and better understand the pathogenesis of COVID-19. SARS-COV-2, ACE2 and TMPRSS2 co-receptors are highly expressed in placental tissues and may be actively involved in transplacental transmission of the virus. From a case of materno-fetal transmission described by our team (publication in progress), we observed placental expression of the Spike SARS-COV-2 protein, but also of the ACE2 receptors, TMPRSS2 and cathepsin L. Cytotrophoblast and syncytiotrophoblast cell stains were positive within the placental villi. Maternal leukocytes were also labeled for these proteins.

Official Title
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Prospective Evaluation of Transplacental Transmission of SARS-COV-2 (COVID-19) in a Cohort of 10 Mother/Child Dyads

Conditions
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SARS-COV-2 Infection

Intervention / Treatment
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* Other: Samples concern SARS-COV-2 + pregnant women at the time of childbirth
* Other: Samples concern newborns of SARS-COV-2 + mothers at birth


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Social security affiliation Signed informed consent Pregnant woman with proven SARS-COV-2 infection during full-term delivery Exclusion Criteria: Patient vaccinated within 15 days prior to inclusion

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| mothers infected with SARS-COV-2 at the time of delivery.<br>Maternal-fetal transmission of SARS-COV-2 is likely and may require co-expression of the virus receptor (ACE2) and at least one activator of virus internalization (TMPRSS2 and/or cathepsin) in a cell to make it susceptible to SARS-COV-2 infection. To confirm these hypotheses, it is necessary to explore these mechanisms of fetal transmission in a larger number of mothers infected with SARS -CoV-2 at the time of delivery. Informed information will be given in the delivery room, initially orally by the midwives, to any mother presenting with an SARS-COV-2 infection (symptomatic or not) (whatever the variant involved). An information leaflet will also be given to the patient and consent will be systematically obtained. | Other: Samples concern SARS-COV-2 + pregnant women at the time of childbirth<br>* nasopharyngeal PCR in the mother (performed systematically in this epidemic context), Blood samples: 1 EthyleneDiamineTetraacetic Acid (EDTA) tube (immunohistochemistry), 1 yellow tube (COVID + RT-qPCR serology). Sampling of amniotic fluid in case of cesarean section Sampling of the placenta for histological and virological study.<br>Other: Samples concern newborns of SARS-COV-2 + mothers at birth<br>* In the birth room: Collection of gastric fluid (PCR SARS-COV-2), Cord blood: 1 EDTA tube (immunohistochemistry), 1 yellow tube (SARS-COV-2 + RT-qPCR serology). In the newborn at D3 of life: - 1 yellow tube (SARS-COV-2 + RT-qPCR serology) at the same time as the DNN. In symptomatic newborns: 1 yellow tube (SARS-COV-2 + RT-qPCR serology). nasopharyngeal PCR,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spike SARS-COV-2 protein in placental tissues | number of cells expressing the Spike SARS-COV-2 protein | Baseline : childbirth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACE2 receptors in placental tissues | number of cells expressing the ACE2 receptors | Baseline : childbirth | 
| TMPRSS2 in placental tissues | number of cells expressing the TMPRSS2 | Baseline : childbirth | 
| cathepsin L in placental tissues | number of cells expressing the cathepsin L | Baseline : childbirth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPRSS2, immune response, SARS-COV-2, ACE2 receptors, cathepsin L