Like a handful of other viruses, the novel coronavirus may also be capable of crossing the placental barrier in pregnant women and infecting the fetus. A recent study from researchers at ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH) and Indian Institute of Science (IISc), Bengaluru, has examined molecular players in the placenta which may be responsible for allowing the virus to access the developing fetus.
Multiple reports of mother to child infection of the novel coronavirus (SARS-CoV‑2) have led scientists to probe how the virus enters the fetus within the womb. A recent study has found that a subset of cells in the placenta may be responsible for allowing SARS-CoV‑2 entry into the developing fetus.
This study was led by Deepak Modi’s team at the Molecular and Cell Biology Laboratory, ICMR-National Institute for Research in Reproductive Health (ICMR-NIRRH) in collaboration with Mohit Kumar Jolly’s group at Indian Institute of Science (IISc), Bengaluru.
“COVID-19 has affected many and pregnant women are not spared. While the major focus of research is on the general population, studies in pregnant women are widely ignored. The main idea of this study was to investigate if coronavirus infection from the mother can be passed on to the baby,” says Deepak Modi.
The placenta is an organ that develops inside the uterus during pregnancy. It connects the mother and the baby via the umbilical cord and acts as a sieve that allows only a select few substances (e.g. nutrients) to pass through while keeping harmful substances (including pathogens) at bay. But just like certain other viruses (e.g. HIV), SARS-CoV‑2 appears to be capable of crossing this placental barrier, resulting in several cases of newborn babies contracting the disease from their infected mothers.
For the placenta to be permissive to the virus, host cells located within it must express a binding receptor protein to which the virus can attach. After attaching, the virus and the host cell membranes must fuse so that the virus can insert its genetic material into the host cell. For this fusion and release process to occur, certain protein-degrading enzymes — proteases — must be produced by the host. Once inside the host cell, the virus hijacks the host’s cellular processes to multiply. Together, these molecules constitute the machinery of virus entry and multiplication. The main goal of the current study was to determine if this machinery is present in the placenta.
The researchers studied the publicly available single-cell RNA sequencing data for COVID-19 and analyzed the levels of mRNA coding for the proteins that are known to be involved in the transport of the virus into the host cell. They also looked for the mRNA coding for proteins involved in its multiplication.
The study revealed that the requisite machinery is expressed in the placenta right from the first trimester. The mRNAs coding for the SARS-CoV‑2 binding receptor (ACE2) and the proteases needed for viral entry and proteins needed for viral multiplication were found to be expressed by certain subtypes of placental cells, which are involved in key placental functions. The study also found receptors to other coronaviruses such as Middle East Respiratory Syndrome (MERS).
Moreover, based on a systematic review of data from 93 pregnant women with COVID-19, the researchers could show that within this cohort, nearly 12% had placental infection with SARS-CoV‑2, suggesting a possibility of mother-to-child transmission of the virus.
Gayatri Venkataraman, Oby-Gynaecologist, Gupte Hospital and Centre for Research in Reproduction, Pune, who was not part of the study says, “Prevention is better than cure, as always…and more so in pregnancy. The study, if continued [on] all 3 elements in pregnancy, i.e. mother, fetus, placenta, may come up with newer causes of miscarriage, pregnancy mishaps and…birth defects via a toxic effect.”
Along with Smita Mahale, Director, ICMR-NIRRH, and Rahul Gajbhiye, Scientist, ICMR-NIRRH, Modi has started a registry for pregnant women with the idea of getting insights into their clinical presentation and health outcomes of COVID-19. Talking about the next steps in this research, Modi says, “We are also studying the placenta of pregnant women in different trimesters to study the impact of maternal COVID-19 and identify the determinants of vertical transmission.”
The study suggests that SARS-CoV‑2 may be detrimental in pregnancy, given its ability to infect the placenta, potentially affecting its function and crossing it to infect the fetus. It suggests a need for special care and attention to be dedicated to protecting pregnant women from the infection.