SARS-CoV-2 Viral Pseudoparticles Preferentially Infect Ectoderm In Human Embryonic Tissues

Abstract

Early stages in human development are difficult to study in pregnant women. We used a "disease-in-a-dish" model to investigate SARS-CoV-2 infection of human embryonic stem cells and the three germ layers. Ectoderm had a significantly higher infection than the other cell types. This was due to: (1) the use of two entry pathways by the ectoderm (fusion and endocytosis), (2) high levels of TMPRSS2 in the ectoderm, and (3) a much-reduced ectodermal glycocalyx, which facilitated viral attachment to the ACE2 receptor. Our findings provide strong evidence that cells in young postimplantation human embryos are susceptible to SARS-CoV-2 infection, which could be embryo lethal or teratogenic in surviving embryos. The high level of infection in ectoderm is a concern as its derivatives may also be affected by SARS-CoV-2. Future clinical work should investigate the functioning of the nervous system in infants born to mothers who had COVID-19 during pregnancy. HighlightsSARS-CoV-2 pseudoparticles infected human embryonic stem cells, endoderm, mesoderm and ectoderm Ectoderm was significantly more susceptible to infection than the other three cell types Factors accounting for increased susceptibility and tissue tropism were identified SARS-CoV-2 virus can adversely affect early stages of human development