Spatial transcriptomics unveils the in situ cellular and molecular hallmarks of the lung in fatal COVID-19
Abstract
Severe Coronavirus disease 2019 (COVID-19) can induce progressive diffuse alveolar damage (DAD) leading to fatal outcomes. Here, we leveraged data from Visium spatial transcriptomics for COVID-19 and control lung samples to unravel insights into cellular and molecular events driving lethal COVID-19. We report a progressive loss of endothelial cell types, pneumocytes type I and natural killer cells coupled with a continuous increase of myeloid and stromal cells, mostly peribronchial fibroblasts, across acute and proliferative DAD. Spatial organization analysis also identified specific compartmentalization including immune-specific clusters across DAD patterns. Importantly, spatially informed ligand-receptor interaction analysis revealed intercellular communication signatures defining COVID-19 induced DAD. Transcription factor activity enrichment analysis identified the TGF-β pathway as DAD driver, highlighting the antagonizing roles of SMAD3 and SMAD7 activity during fibrosis. Integration of these data yielded a signaling kinase pathway in peribronchial fibroblasts with amenable novel targets. Finally, spatio-temporal trajectory analysis characterized an alveolar epithelium regeneration program.
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BibTeX
@article{garciaprieto2026spatial,
title = {{Spatial transcriptomics unveils the in situ cellular and molecular hallmarks of the lung in fatal COVID-19}},
author = {Carlos A. Garcia-Prieto and Eva Musulen and Daniela Grases and Veronica Davalos and Gerardo Ferrer and Belén Pérez-Miés and Tamara Caniego-Casas and José Palacios and Xavier Saenz-Sardà and Elisabet Englund and Eduard Porta and Manel Esteller},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78188-3},
url = {https://www.nature.com/articles/s41467-026-78188-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Spatial transcriptomics unveils the in situ cellular and molecular hallmarks of the lung in fatal COVID-19
AU - Carlos A. Garcia-Prieto
AU - Eva Musulen
AU - Daniela Grases
AU - Veronica Davalos
AU - Gerardo Ferrer
AU - Belén Pérez-Miés
AU - Tamara Caniego-Casas
AU - José Palacios
AU - Xavier Saenz-Sardà
AU - Elisabet Englund
AU - Eduard Porta
AU - Manel Esteller
PY - 2026
DA - 2026/10/15
JO - Nature Communications
DO - 10.1038/s41467-026-78188-3
UR - https://www.nature.com/articles/s41467-026-78188-3
AB - Severe Coronavirus disease 2019 (COVID-19) can induce progressive diffuse alveolar damage (DAD) leading to fatal outcomes. Here, we leveraged data from Visium spatial transcriptomics for COVID-19 and control lung samples to unravel insights into cellular and molecular events driving lethal COVID-19. We report a progressive loss of endothelial cell types, pneumocytes type I and natural killer cells coupled with a continuous increase of myeloid and stromal cells, mostly peribronchial fibroblasts, across acute and proliferative DAD. Spatial organization analysis also identified specific compartmentalization including immune-specific clusters across DAD patterns. Importantly, spatially informed ligand-receptor interaction analysis revealed intercellular communication signatures defining COVID-19 induced DAD. Transcription factor activity enrichment analysis identified the TGF-β pathway as DAD driver, highlighting the antagonizing roles of SMAD3 and SMAD7 activity during fibrosis. Integration of these data yielded a signaling kinase pathway in peribronchial fibroblasts with amenable novel targets. Finally, spatio-temporal trajectory analysis characterized an alveolar epithelium regeneration program.
SN - 2041-1723
ER -