SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues

The early stages of human embryonic development are challenging to study in pregnant women.

A "disease-in-a-dish" model was utilized to investigate SARS-CoV-2 infection of human embryonic stem cells and the three germ layers (ectoderm, endoderm, and mesoderm).

Ectodermal cells showed significantly higher infection rates compared to the other cell types. This increased susceptibility was attributed to three key factors characteristic of the ectoderm: dual viral entry pathways (membrane fusion and endocytosis), elevated TMPRSS2 activity, and a markedly reduced glycocalyx, which facilitated viral access to host cell receptors.

Our findings provide strong evidence that cells in early post-implantation human embryos are susceptible to SARS-CoV-2 infection. The high level of infection in the ectodermal cells raises concern for potential teratogenic effects, particularly involving the nervous system. Future clinical studies should investigate neurological outcomes in infants born to mothers infected with SARS-CoV-2 during pregnancy.