Scientists explore triggers associated with transplacental transmission of SARS-CoV-2

With the early reports of a new coronavirus from spreading rapidly and causing severe pneumonic disease among the affected, there was much panic, and mass-scale economically disruptive public health containment measures were implemented. This continued for over two years as the coronavirus disease 2019 (COVID-19) pandemic continues to prevail.

A new study to be published in the American Journal of Obstetrics and Gynecology examines the risk of fetal infection following the infection of a pregnant mother with the virus.

Introduction

Early on, pregnancy was identified as a high-risk group for protection against infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pregnant women and their offspring were thought to be at greater risk for severe disease and for associated complications from COVID-19, including pre-eclampsia, stillbirth, preterm birth and birth by Cesarean section.

Initially, this led to many and elaborate precautions to prevent vertical transmission of the virus. However, a few reports surfaced of the detection of viral ribonucleic acid (RNA) in the fetal serum, indicating that transplacental transmission had occurred. This is possible through the Hofbauer cells, the macrophages of the placenta.

The current study looked into the role played in such transmission by the placental expression of receptors for the virus, the viral load, the degree of inflammation and the clinical features that may be involved.

The study was based on six cases with transplacental transmission where the placenta tested positive for the viral RNA by polymerase chain reaction (PCR). The first case showed fetal distress, leading to the monitoring of all subsequent pregnancies. In addition, there were four women who had positive placental PCR tests but no transplacental transmission, following third-trimester COVID-19.

As controls, there were 10 women with third-trimester COVID-19 but no placental infection, that is, a negative placental PCR, and 11 pregnancies with no SARS-CoV-2 infection.

Using a combination of techniques, including enzyme-linked immunosorbent assay for viral receptors, PCR to detect the viral load, gene sequencing, placental histology and immunohistochemistry, the researchers examined the placentas in all groups, adding in the clinical data.

Findings

All patients with COVID-19 had mild to moderate disease. Of the six transplacental transmissions, one neonate developed cerebral vasculitis and another died in utero. The others developed normally. All had definite placental infections, three with the ancestral and three with the Alpha variant of the virus.

The incidence of fetal distress was higher among surviving babies, as was the need for Cesarean delivery and admission to the neonatal intensive care unit (NICU), even though all mothers had similar viral loads and expressed viral receptors on the placenta at comparable levels.

All cases where the baby was born infected with the virus because of transplacental transmission were either premature or had non-reassuring fetal heart tracings, despite their mothers having only mild or moderate symptoms.

In cases with transplacental transmission, the placenta showed fibrin deposits around the placental villi on a large scale in over half of the tissue, compared to <40% in other placentas. Similarly, intervillositis was observed to occur diffusely, along with fibrin deposits and necrosis in the former cohort. Finally, SARS-CoV-2 nucleoprotein was detected at the villous surface in these placentas.

Implications

The findings of this study suggest that transplacental transmission is not linked to the viral load or the expression of the viral receptors on the placental tissue. However, when it occurs, the placenta appears to show a unique pattern of fibrin deposition and diffuse inflammation. Fetal monitoring also shows deterioration of the baby.

While there is no present evidence for recommending fetal monitoring during all cases when the pregnant woman has mild to moderate COVID-19, these findings do suggest that transplacental transmission might be more common in such a situation than is thought. The primary risk for transplacental transmission could be the occurrence of maternal infection close to the time of delivery.

The reason for this may be the inflammatory damage to the placenta, linked to the immune response at the interface of fetal and maternal tissue in this organ, along with rising levels of cytokines in the fetal blood. This could correspond to the cytokine storm seen in severe COVID-19. In the current situation, this could cause a hyperactive local response, which in turn leads to placental insufficiency, allowing the virus to cross the placenta.

This is the first study in this situation that provides a control group to understand the mechanisms whereby the virus crosses the placenta. Despite the small group size and the lack of knowledge as to the variants responsible, these findings merit further follow-up in larger studies and point to a larger incidence of transplacental transmission even in women with mild to moderate COVID-19.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.