System-wide transcriptome damage and tissue identity loss in COVID-19 patients
Wurtele, Eve Syrkin
Is Version Of
Genetics, Development and Cell BiologyBioinformatics and Computational Biology
The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.
This article is published as Park, Jiwoon, Jonathan Foox, Tyler Hether, David C. Danko, Sarah Warren, Youngmi Kim, Jason Reeves et al. "System-wide transcriptome damage and tissue identity loss in COVID-19 patients." Cell Reports Medicine 3 (2022): 100522. doi:10.1016/j.xcrm.2022.100522. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
coronavirus, evere acute respiratory syndrome coronavirus 2, SARS-CoV-2, spatial transcriptomics, coronavirus disease 2019, COVID-19, next-generation sequencing, NGS, RNA-seq, host response