Journal
CELL REPORTS MEDICINE
Volume 3, Issue 12, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.xcrm.2022.100849
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Funding
- National Key Research and Development Program of China [2018YFA0902702]
- ITC Health@InnoHK
- Na-tional Natural Science Foundation of China [81570202, 32100639, 82071856, 816715793, 1370904]
- Health and Medical Research Fund
- Food and Health Bureau
- Government of the HKSAR [COVID190114, 09202056]
- Hong Kong Research Grant Council [C7142-20GF, GRF 17127219, 17126421, 17112422, GRF 17112822]
- China Post-doctoral Science Foundation [2021M702280]
- Health Commission of Guangdong Province [HKUSZH201902025, HKUSZH201902037, HKUSZH201902008]
- Program for Scientific and Technological Innovation from the Science and Technology Commission of Shanghai Municipality [22490760400]
- HKU
- HKU Shenzhen Hospital
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Human placenta trophoblasts and their derivatives are susceptible to SARS-CoV-2 infection, with early syncytiotrophoblasts displaying high infectivity. These findings highlight the potential risk of COVID-19 infection during embryonic implantation.
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 SARSCoV-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.
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