Human Early Syncytiotrophoblasts Are Highly Susceptible to SARS-CoV-2 Infection. Ruan et al
Direct in vivo investigation of human placenta trophoblast’s susceptibility to SARS-CoV-2 is challenging. Here we report that human trophoblast stem cells (hTSCs) and their derivatives are susceptible to SARS-CoV-2 infection which reveal heterogeneity in hTSC cultures. Early syncytiotrophoblasts (eSTBs) generated from hTSCs have enriched transcriptomic features of peri-implantation trophoblasts, express high levels of angiotensin-converting enzyme 2 (ACE2) and are productively infected by SARS-CoV-2 and its Delta and Omicron variants to produce virions. Antiviral drugs suppress SARS-CoV-2 replication in eSTBs and antagonize the virus-induced blockage of STB maturation. Though less susceptible to SARS-CoV-infection, viral replication in trophoblast organoids originated from hTSCs are detectable, reminiscent of the uncommon placenta infection. These findings implicate possible risks of COVID-19 infection in peri-implantation embryos which may go unnoticed. Stem cell-derived human trophoblasts such as eSTBs can potentially provide unlimited amounts of normal and genome-edited cells and facilitate coronavirus research and antiviral discovery.