Recently doctors in Pune confirmed that it was possible for a Covid-19 infected pregnant woman to transmit the virus to her baby through the placenta. The Indian Council of Medical Research (ICMR)-National Institute of Research in Reproductive Health (NIRRH), Parel, too have revealed this possibility, after a recent finding. While the mother-to-child transmission has only been found in one per cent of the total 15,000 childbirths in Maharashtra, the finding is likely to give birth to a new debate. The overall vertical transmission rate of SARS-CoV-2 is estimated to be eight per cent, according to the study by ICMR-NIRRH.
The SARS-CoV-2 infection during pregnancy is associated with complications such as pre-term labour and premature rupture of membranes, and a proportion of newborns of infected mothers are also found positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development.
The authors of the study are Dr Smita Mahale, director, ICMR-NIRRH, Dr Deepak Modi, head of molecular and cellular biology laboratory, ICMR-NIRRH, Dr Mohit Kumar Jolly, IISC, students Nancy Ashary and Anshul Bhide.
To predict if the placenta is permissible to SARS-CoV-2, researchers from the ICMR-NIRRH, along with the Indian Institute of Science (IISc), Bengaluru, conducted a secondary data study, titled “Single-Cell RNA-sea Identifies Cell Subsets in Human Placenta That Highly Expresses Factors Driving Pathogenesis of SARS-COV-2” from published literature in the UK and the USA.
Though there is a current belief that there is no vertical transmission (from infected mother to the fetus) of the virus, researchers have found the presence of the virus in 12 per cent of 93 infected women from other published literature in the UK and US.
In the throat and lungs, SARS-Cov-2 enters the cells through a gateway or receptors called ACE2. The researchers used publicly available single-cell RNA-seq data to identify if the placental cells express the necessary factors required for infection. The SARS-CoV-2 binding receptor ACE2 and the S protein-priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra-villous trophoblasts (EVT) in the second trimester human placenta.
Dr Deepak Modi, head of molecular and cellular biology laboratory, ICMR-NIRRH and the author of the study said to address the extent of maternal to fetal transmission of SARS-CoV-2, they carried out a sub-group analysis where they compiled data from the publications that explicitly reported the neonatal SARS-CoV-2 testing by the type of laboratory method used (RT-PCR or antibody or both), the neonatal samples tested and the time of testing. "We further employed a strict criterion to select those studies where the diagnosis was confirmed by RT-PCR only within the first 48 hours of life and where the source of sampling was clearly mentioned," Dr Modi said.
“We found that the cells of the placenta express ACE2. Other than this, the cells also express another novel coronavirus receptor, called BSG or CD147. The researchers also found the placenta has receptors for other coronaviruses like the Middle East Respiratory Syndrome (MERS),” he said
“For the virus to enter inside the cells, the spike protein (also called S protein) of the virus has to get sliced which occurs by the use of enzymes called as transmembrane serine protease TMPRSS2 and cathepsin. We have found that along with ACE2, the cells of the placenta express the enzymes TMPRSS2, Cathepsins and Furin. These results provide a piece of strong evidence of the possibility of SARS-CoV-2 infecting the placenta,” Dr Modi added.
The study also shows that if the virus enters the placental cells it will reproduce inside them as the cells have the necessary machinery for viral replication. These results imply that not only can the placenta get infected with the virus, it will also be spread around locally.
“There is a strong likelihood that if the placenta harbours viral infection, it may be passed to the baby. Although SARS-CoV-2 is not a blood-borne virus, in some cases, when the virus seeps into the mother’s blood, it will reach the placenta,disseminating infection,” said Dr Modi.
However, the authors have suggested that obstetricians need to closely monitor these patients and study the placenta carefully as the possibility is not as rare as it is believed to be. These findings have important health implications on pregnancy and Covid-19.
Dr Mahale said there were many cases of newborns getting infected or diagnosed with Covid-19 but there is no evidence of the source through which they got infected. “To know the source, we decided to conduct a study for which we needed research papers and data. Just like RT-PCR that helps to diagnose the presence of Sars-Cov-2 among people, we planned to test placentas to identify the virus,” she said.