Human early syncytiotrophoblasts are highly susceptible to SARS-CoV-2 infection
Degong Ruan, Zi‐Wei Ye, Shuofeng Yuan, Zhuoxuan Li, Weiyu Zhang, Chon Phin Ong, Kaiming Tang, Timothy Theodore Ka Ki Tam, Jilong Guo, Yiyi Xuan, Yunying Huang, Qingqing Zhang, Cheuk‐Lun Lee, Liming Lu, Philip C.N. Chiu, William S.B. Yeung, Fang Liu, Dong‐Yan Jin, Pentao Liu
Abstract
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 reveals 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. Although less susceptible to SARS-CoV-2 infection, trophoblast organoids originating from hTSCs show detectable viral replication reminiscent of the uncommon placental infection. These findings implicate possible risk 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.