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

Song et al., Frontiers in Cell and Developmental Biology, doi:10.3389/fcell.2026.1733662, Apr 2026
In vitro study showing that SARS-CoV-2 pseudoparticles preferentially infect ectodermal cells derived from human embryonic stem cells (hESCs), with ectoderm showing ~23-fold greater infection than undifferentiated hESCs and ~6-fold greater infection than mesoderm.
Song et al., 7 Apr 2026, Canada, peer-reviewed, 2 authors. Contact: talbot@ucr.edu.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: OPEN ACCESS Biomedical Research Institute of Southern EDITED BY Prasad S. Koka, California, United States REVIEWED BY Hao Wu, Chinese Academy of Sciences (CAS), China O. Greer, Imperial College London, United Kingdom *CORRESPONDENCE Prue Talbot, talbot@ucr.edu RECEIVED 27 October 2025 REVISED 22 February 2026 ACCEPTED 25 February 2026 PUBLISHED 07 April 2026 CITATION Song A and Talbot P (2026) SARS-CoV2 pseudoparticles preferentially infect ectoderm in human embryonic tissues. Front. Cell Dev. Biol. 14:1733662. doi: 10.3389/fcell.2026.1733662 COPYRIGHT © 2026 Song and Talbot. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. [SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues](https://www.frontiersin.org/articles/10.3389/fcell.2026.1733662/full) Ann Song 1,2 and Prue Talbot 2 * 1 Cell, Molecular, and Developmental Biology Graduate Program, University of California, Riverside, CA, United States, 2 Department of Molecular, Cell, and Systems Biology, University of California, Riverside, CA, United States Introduction: The early stages of human embryonic development are challenging to study in pregnant women. Methods: A 'disease-in-a-dish' model was utilized to investigate SARS-CoV2 infection of human embryonic stem cells and the three germ layers (ectoderm, endoderm, and mesoderm). Results: 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. Discussion: Our findings provide strong evidence that cells in early postimplantation 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. KEYWORDS COVID-19, disease-in-a-dish, ectoderm, embryonic stem cells, SARS-CoV-2, teratogens, tropism
DOI record: { "DOI": "10.3389/fcell.2026.1733662", "ISSN": [ "2296-634X" ], "URL": "http://dx.doi.org/10.3389/fcell.2026.1733662", "abstract": "<jats:sec>\n <jats:title>Introduction</jats:title>\n <jats:p>The early stages of human embryonic development are challenging to study in pregnant women.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>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).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Discussion</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>", "alternative-id": [ "10.3389/fcell.2026.1733662" ], "article-number": "1733662", "author": [ { "affiliation": [ { "name": "Cell, Molecular, and Developmental Biology Graduate Program, University of California", "place": [ "Riverside, CA, United States" ] }, { "name": "Department of Molecular, Cell, and Systems Biology, University of California", "place": [ "Riverside, CA, United States" ] } ], "family": "Song", "given": "Ann", "sequence": "first" }, { "affiliation": [ { "name": "Department of Molecular, Cell, and Systems Biology, University of California", "place": [ "Riverside, CA, United States" ] } ], "family": "Talbot", "given": "Prue", "sequence": "additional" } ], "container-title": "Frontiers in Cell and Developmental Biology", "container-title-short": "Front. Cell Dev. 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