System-wide transcriptome damage and tissue identity loss in COVID-19 patients

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  • Park, Jiwoon
    • Other Affiliation: Weill Cornell Medicine
  • Foox, Jonathan
    • Other Affiliation: Weill Cornell Medicine
  • Hether, Tyler
    • Other Affiliation: NanoString Technologies, Inc
  • Danko, David C.
    • Other Affiliation: Weill Cornell Medicine
  • Warren, Sarah
    • Other Affiliation: NanoString Technologies, Inc
  • Kim, Youngmi
    • Other Affiliation: NanoString Technologies, Inc
  • Reeves, Jason
    • Other Affiliation: NanoString Technologies, Inc
  • Butler, Daniel J.
    • Other Affiliation: Weill Cornell Medicine
  • Mozsary, Christopher
    • Other Affiliation: Weill Cornell Medicine
  • Rosiene, Joel
    • Other Affiliation: New York Genome Center
  • Shaiber, Alon
    • Other Affiliation: New York Genome Center
  • Afshin, Evan E.
    • Other Affiliation: Weill Cornell Medicine
  • MacKay, Matthew
    • Other Affiliation: Weill Cornell Medicine
  • Rendeiro, André F.
    • Other Affiliation: Weill Cornell Medicine
  • Bram, Yaron
    • Other Affiliation: Weill Cornell Medicine
  • Chandar, Vasuretha
    • Other Affiliation: Weill Cornell Medicine
  • Geiger, Heather
    • Other Affiliation: New York Genome Center
  • Craney, Arryn
    • Other Affiliation: Weill Cornell Medicine
  • Velu, Priya
    • Other Affiliation: Weill Cornell Medicine
  • Melnick, Ari M.
    • Other Affiliation: Weill Cornell Medicine
  • Hajirasouliha, Iman
    • Other Affiliation: Weill Cornell Medicine
  • Beheshti, Afshin
    • Other Affiliation: NASA Ames Research Center
  • Taylor, Deanne
    • Other Affiliation: The Children's Hospital of Philadelphia
  • Saravia-Butler, Amanda
    • Other Affiliation: NASA Ames Research Center
  • Singh, Urminder
    • Other Affiliation: Iowa State University
  • Wurtele, Eve Syrkin
    • Other Affiliation: Iowa State University
  • Schisler, Jonathan
    • Affiliation: School of Medicine, UNC McAllister Heart Institute
  • Fennessey, Samantha
    • Other Affiliation: New York Genome Center
  • Corvelo, André
    • Other Affiliation: New York Genome Center
  • Zody, Michael C.
    • Other Affiliation: New York Genome Center
  • Germer, Soren
    • Other Affiliation: New York Genome Center
  • Salvatore, Steven
    • Other Affiliation: Weill Cornell Medicine
  • Levy, Shawn
    • Other Affiliation: HudsonAlpha Discovery Institute
  • Wu, Shixiu
    • Other Affiliation: Hangzhou Cancer Hospital
  • Tatonetti, Nicholas P.
    • Other Affiliation: Columbia University
  • Shapira, Sagi
    • Other Affiliation: Columbia University
  • Salvatore, Mirella
    • Other Affiliation: Weill Cornell Medicine
  • Westblade, Lars F.
    • Other Affiliation: Weill Cornell Medicine
  • Cushing, Melissa
    • Other Affiliation: Weill Cornell Medicine
  • Rennert, Hanna
    • Other Affiliation: Weill Cornell Medicine
  • Kriegel, Alison J.
    • Other Affiliation: Medical College of Wisconsin
  • Elemento, Olivier
    • Other Affiliation: Weill Cornell Medicine
  • Imielinski, Marcin
    • Other Affiliation: Weill Cornell Medicine
  • Rice, Charles M.
    • Other Affiliation: Weill Cornell Medicine
  • Borczuk, Alain C.
    • Other Affiliation: Weill Cornell Medicine
  • Meydan, Cem
    • Other Affiliation: Weill Cornell Medicine
  • Schwartz, Robert E.
    • Other Affiliation: Weill Cornell Medicine
  • Mason, Christopher E.
    • Other Affiliation: Weill Cornell Medicine
Abstract
  • 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., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung.
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Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 4.0 International
Journal title
  • Cell Reports Medicine
Journal volume
  • 3
Journal issue
  • 2
Page start
  • 100522
Language
  • English
Version
  • Publisher
ISSN
  • 2666-3791

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