COVID-19 can infect pregnant women's placenta, finds ICMR Study

The authors said their work is the first in-depth survey to identify the cellular basis of Sars-CoV-2 infection in the human placenta, and therefore assumes importance because it will help to establish the fact that cross transmission from the infected mothers to the children is possible.

Analysing a database of RNA (ribonucleic acid) sequences of human placenta, the eight-member team said there is strong likelihood that the novel coronavirus infection can be passed on to the foetus because the placental cells possess the same receptors that the Sars-CoV-2 virus uses to attach itself in throat and lungs cells of Covid-19 patients.

Since the global outbreak of the pandemic, the scientific community has been trying to establish whether Sars-CoV-2 can infect placenta. In Maharashtra, more than 15,000 pregnant women have contracted Covid-19 since the outbreak of the novel coronavirus infection in March, of which new born babies were diagnosed with Covid-19 in less than 1% of the cases. However, the researchers plan clinical studies to test placenta of Covid-19 pregnant women for conclusive evidence.

"During pregnancy, the foetus is protected from maternal infections by the placenta. The placenta is an organ that develops during pregnancy and provides oxygen and nutrients to the growing baby, removes waste products and also blocks transmission of the infections from mother to the baby by creating a barrier," said Dr Deepak Modi, head of Molecular and Cellular Biology Laboratory, ICMR-NIRRH.

"However, the barrier can break if placental cells get infected, leading to mother-to-child transmission," said Dr Modi, who was a part of the study.

The study 'Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That highly Expresses Factors Driving Pathogenesis of SARS-COV-2' was published in Frontiers of Cell and Developmental Biology journal on August 19.

The team conducted a secondary data study from an existing database of placental cell RNA (Ribonucleic Acid) sequences (published from the USA) to find if the RNA for coronavirus receptors are present in the placental cells. RNA is ribonucleic acid that is essential in various biological roles in coding, decoding, regulation and expression of genes.

While the current assumption is that there is no vertical transmission of the virus from the infected mother to the foetus, researchers found the presence of the virus in 12% of the 93 infected women from other published literature in the UK and US. They came to this conclusion after a systematic analysis said Anshul Bhide a co-first author in the study.

The team found that cells of the placenta express ACE2 receptors – the same receptor that the Sars-CoV-2 virus uses to enter the cells in the throat and lungs of an individual who is infected with the novel coronavirus.

"Additionally, the placental cells also express another novel coronavirus receptor called BSG or CD147. We also found that the placenta has receptors of other coronaviruses like Middle East respiratory syndrome (MERS)", said Nancy Ashary, the first author of the study.

"For the virus to enter inside the cells, the Spike protein (also called as S protein) of the virus has to get sliced, which occurs by the use of enzymes called 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 strong evidence for the possibility of Sars-CoV-2 to infect the placenta," said Dr Modi.

The study also shows that if the virus enters the placental cells it will reproduce inside them as these cells have the necessary machinery for viral replication. These results imply that the placenta can not only get infected with the virus, but will also spread around locally.

"There is a strong likelihood that if the placenta harbours viral infection it may be passed to the baby. Sars-CoV-2 is not a blood borne virus. But if in some cases the virus seeps into the mother's blood, it will reach the placenta disseminating infection," said Modi.

With the identification of viral receptors in placenta, researchers have suggested that obstetricians need to closely monitor the infected pregnant women and study the placenta carefully since the possibility of the presence of the virus may not be as rare as it is believed to be.

"We often hear that newborns have been diagnosed with Covid-19, but we don't know the source of infection. It can be through the infected mother but also through horizontal transmission ie. hospital acquired infection," said Dr Smita Mahale, Director, ICMR-NIRRH. "Just like reverse transcription polymerase chain reaction (RT-PCR) tests that help diagnose the presence of Sars-CoV-2, we plan to test placentas to identify the virus."

Mohit Kumar Jolly, co-author and assistant professor, Centre for BioSystems Science and Engineering, IISC, said, "Our study clearly shows that the organ (placenta) has molecular structures which get attached to the virus. There is also a possibility that the infection can spread to other parts of the body through placenta due to the presence of certain cells. But since this is a secondary data based study, we can't say what percent of women in India are getting Covid-19 infection in their placenta."

Dr Aparna Hedge, head, division of urogynaecology at Cama Hospital, Grant Medical College, who was not a part of the study, said, "Even though it is not a clinical study, it provides a perspective of the possible spread of the virus in placenta. There have been several debates on it but no scientifically proven evidence is available. We need more clinical-based studies to establish any fact."

"The pilot results from the study are likely to be of immense help in understanding the role of Sars-CoV-2 infection of the human placenta and its consequences on pregnancy outcome and vertical transmission. Their study is amply supported by another recent publication 'The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study'. This ACE2 expression was still detected at 24 weeks of gestation. The high expression of ACE2 in these cells suggests that the placenta has the potential to be infected by Sars-CoV-2 and may cause placental dysfunction and pregnancy complications," said Surendra Sharmam, director, Center of Excellence for Reproductive Health, Women and Infants Hospital, Brown University and editor-in-chief, American Journal of Reproductive Immunology.