Factors Influencing SARS-CoV-2 Transplacental Transmission

Background: SARS-CoV-2 transplacental transmission is a rare event that can lead to relevant negative consequences for the offspring. The factors influencing transplacental transmission are unclear: we designed a study to verify whether placental expression of viral receptors, viral load, inflammation, or some clinical features influence SARS-CoV-2 transplacental transmission. Methods: We enrolled women diagnosed with COVID-19 during the third trimester, with (C+P+ group, n=10) or without (C+P- group, n=10) positive RT-PCR on placental tissue, and pregnant women without SARS-CoV-2 infection (Control group, n=11). Six cases of SARS-CoV-2 transplacental transmission were included in the C+P+ group. Investigators blinded to clinical data performed protein assay, ELISA for ACE2 and TMPRSS2 receptors, viral load estimation and Sanger sequencing, pathology examination with immunohistochemistry on placental specimens. Clinical data were real time collected and masked to investigators performing laboratory assays. Findings: We found that transplacental transmission of SARS-CoV-2 is not related to the placental expression of ACE2 (p=0·335) and TMPRSS2 (p=0·163) receptors or viral load (p=0·153) or any common clinical perinatal characteristics. Transplacental transmission was associated with placental inflammation, and particularly with intervillositis with peculiar pathological signature (massive fibrin deposition, diffuse chronic intervillositis with necrosis and positive viral staining in the intervillositis lesions), which may damage the placental barrier and is associated with foetal distress (p =0·002), acidosis at the birth (p =0·038) and need for neonatal intensive care (p =0·008). Interpretation: Transplacental SARS-CoV-2 transmission is associated with placental inflammation and seems to occur when the placental damage is sufficient to determine foetal distress and acidosis at the birth.Funding: The study was supported by charity grants from the Association for the research development in obstetrics and gynaecology and from the Association for the research and development in neonatology (both lump grants received in 2021).Declaration of Interest: None to declare. Ethical Approval: The study was conducted in agreement with Declaration of Helsinki principles. The protocol was approved by the institutional review board (CEROG 2021-OBST-0102), informed consent (including approval for the use of neonatal data in cases of transplacental transmission) was obtained from all women prior to the enrolment. Data and sample collection was anonymous and respected all relevant local and European regulations.