Unveiling the Mechanism of COVID-19 Transmission to the Placenta

Australian scientists have made a groundbreaking discovery regarding the infection of the human placenta by the COVID-19 virus. Their research reveals that the virus specifically targets syncytiotrophoblast cells, which play a vital role in supporting pregnancy. Furthermore, the study demonstrates that anti-ACE2 antibodies and antiviral medications can effectively prevent this infection. These findings represent a significant advancement in comprehending and potentially mitigating the impact of viral infections on pregnancy.

The groundbreaking study, published on July 13 in the journal Nature Cell Biology, sheds light on how COVID-19 infiltrates the human placenta. Led by Professor Jose Polo from Monash University and Professor Kanta Subbarao from the Peter Doherty Institute for Infection and Immunity, the Australian research team utilized an innovative method developed by Professor Polo and his colleagues. They reprogrammed human skin cells into trophoblast stem cells, which are involved in the attachment of a developing embryo to the uterine wall, ultimately forming the placenta. Through their investigation, they discovered that ACE2, a protein serving as the entry point for SARS-CoV-2 into organs like the lungs, is present in specific placental cells known as syncytiotrophoblasts (ST cells).

The vulnerability of ST cells to the virus is a significant revelation since these placental cells are responsible for producing the crucial hormone for maintaining pregnancy, known as hCG. Infection with SARS-CoV-2 was observed to have a substantial impact on the survival and differentiation of ST cells, resulting in reduced production of hCG. This finding potentially explains the reports of placental inflammation associated with COVID-19, although further research is required to fully understand the implications.

Dr. Joseph Chen, a stem cell biologist at Monash University and co-first author of the study, explained the implications of this discovery. He stated, “Our research demonstrates that SARS-CoV-2 infection significantly impairs the survival and differentiation of ST cells, which leads to a decrease in hCG production. This provides insight into how COVID-19 might affect pregnancy, but further investigation is necessary.”

In addition to elucidating the mechanism of infection, the research team also made a significant breakthrough in preventing the transmission of SARS-CoV-2 to placental cells. Dr. Jessica Neil, a virologist at the Doherty Institute and co-first author of the study, reported that “anti-ACE2 antibodies and antiviral drugs effectively prevented SARS-CoV-2 infection and restored normal differentiation and function of ST cells.”

Professor Subbarao highlighted the broader significance of this study for understanding viral infections during pregnancy. She remarked, “Our findings provide valuable insights into the relationship between SARS-CoV-2 infection and placental pathology. This discovery is a game-changer as it equips us to explore the potential impact of other viruses on the early stages of placental development.”

Professor Polo emphasized the importance of this research in establishing a platform for studying early placental cell types. He said, “This study not only enhances our understanding of the impact of COVID-19 infection on the placenta during pregnancy, but it also provides a versatile and scalable platform for studying early placental cell types.”

The study, titled “A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts,” was published in Nature Cell Biology on July 13, 2023 (DOI: 10.1038/s41556-023-01182-0).

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• Nature Cell Biology: A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts