Transplacental transmission of SARS-CoV-2 infection

The SARS-CoV-2 outbreak, causing COVID-19, primarily spreads through droplets, though other routes are suspected. The possibility and mechanism of mother-to-fetus transmission remain unclear. Understanding this is crucial for preventing neonatal infection, optimizing pregnancy management, and advancing understanding of SARS-CoV-2 biology. This study presents a detailed case demonstrating transplacental SARS-CoV-2 transmission and its clinical manifestation in the neonate, specifically neurological symptoms consistent with COVID-19. The lack of clarity around perinatal transmission necessitates comprehensive investigations to definitively determine the transmission route (transplacental, transcervical, or environmental exposure). This case study aims to fill this knowledge gap.

Several previous studies reported potential perinatal SARS-CoV-2 transmission. However, these studies often lacked crucial elements like detection of the virus in neonates, focused solely on antibody presence, or failed to definitively determine the transmission route due to incomplete testing of placenta, amniotic fluid, and maternal/newborn blood samples. The need for a clear classification system for perinatal SARS-CoV-2 infection became evident, highlighting inconsistencies in case definitions across different studies. Existing research pointed towards the possibility of transplacental transmission but lacked the comprehensive evidence presented in this case study.

This study involved a 23-year-old pregnant woman admitted at 35+2 weeks of gestation with COVID-19 symptoms (fever, cough, expectoration). RT-PCR testing detected SARS-CoV-2 in her blood, nasopharyngeal, and vaginal swabs. Due to a category III fetal heart rate tracing, a Cesarean section was performed. Amniotic fluid, collected prior to membrane rupture, also tested positive for SARS-CoV-2. The neonate (male, 35+5 weeks gestation, 2540g) had low Apgar scores and required resuscitation. RT-PCR testing on cord blood, bronchoalveolar lavage fluid, and nasopharyngeal/rectal swabs confirmed neonatal SARS-CoV-2 infection. On day 3, the neonate developed neurological symptoms (irritability, poor feeding, hypertonia, opisthotonos). Cerebrospinal fluid (CSF) analysis initially showed inflammation but was negative for SARS-CoV-2. MRI at 11 days of life revealed bilateral gliosis. The neonate recovered and was discharged after 18 days. The placenta was also RT-PCR positive for SARS-CoV-2 and showed histological evidence of diffuse peri-villous fibrin deposition, infarction, and acute and chronic intervillositis. Immunostaining confirmed SARS-CoV-2 N-protein positivity in peri-villous trophoblastic cells. Detailed RT-PCR methodology is described including RNA extraction, kit used, cycle threshold values, and limit of detection. Placental examination involved standard procedures adhering to the Amsterdam Consensus statement, including various staining methods and immunohistochemistry for different pathogens.

This case definitively demonstrates transplacental transmission of SARS-CoV-2, based on the positive RT-PCR results in amniotic fluid (collected before membrane rupture), placental tissue, maternal blood, and neonatal blood. The high viral load in the placental tissue (significantly higher than in other samples) strongly suggests active viral replication within the placenta. The placenta exhibited significant inflammation, including intervillositis and fibrin deposition, indicating a robust inflammatory response. The neonate's subsequent development of neurological symptoms (consistent with findings in adult COVID-19 patients), along with MRI evidence of white matter injury, suggests a direct link between the infection and neurological complications. The viral load in the neonate's samples (nasopharyngeal swabs) also increased over time even in the isolated setting, confirming a true infection. The detailed laboratory findings in Table 1 provide a comprehensive overview of the neonate's condition. Figures 1-5 illustrate the fetal heart rate tracing, MRI findings, RT-PCR results, and placental histology/immunohistochemistry results.

This case confirms the possibility of transplacental SARS-CoV-2 transmission during late pregnancy, leading to placental inflammation and neonatal viremia. The neurological manifestations observed in the neonate highlight a potential severe complication of congenital SARS-CoV-2 infection. The high viral load in the placenta suggests active replication, potentially contributing to the observed inflammation. The placental pathology observed is similar to that found in SARS-CoV-1 infections. The expression of ACE2, the SARS-CoV-2 receptor, in placental tissues supports the feasibility of transplacental infection. While this study focuses on late pregnancy, the possibility of earlier transmission cannot be entirely excluded. This study contributes significantly to the understanding of perinatal SARS-CoV-2 transmission, providing strong evidence for transplacental passage, associated inflammation, and the potential for serious neonatal neurological complications.

This study provides compelling evidence of transplacental SARS-CoV-2 transmission, resulting in placental inflammation and neonatal viremia with subsequent neurological symptoms. The findings emphasize the potential severity of congenital SARS-CoV-2 infection and underscore the need for continued research into the mechanisms of transplacental transmission and long-term neurological outcomes in affected neonates. Future research should focus on investigating earlier gestational transmission, the long-term effects on neurodevelopment, and developing effective preventative and treatment strategies.

This study is limited by its single-case design, which prevents generalization of the findings to the broader population. Further studies with larger sample sizes are necessary to confirm the frequency and severity of transplacental transmission and associated neurological complications. The specific mechanisms underlying the neurological manifestations in the neonate require further investigation. While the study comprehensively investigated this case, it is crucial to recognize that this is one instance and more research would be beneficial to establish a broader understanding and patterns.