System-wide transcriptome damage and tissue identity loss in COVID-19 patients
Creators: name: Salvatore, Steven
name: Rice, Charles M.
name: Velu, Priya
name: Kim, Youngmi
name: Westblade, Lars F.
name: Singh, Urminder
name: Foox, Jonathan
name: Rennert, Hanna
name: Elemento, Olivier
name: Meydan, Cem
name: Taylor, Deanne
name: Shapira, Sagi
name: Melnick, Ari M.
name: Imielinski, Marcin
name: Afshin, Evan E.
name: Shaiber, Alon
name: Park, Jiwoon
name: Tatonetti, Nicholas P.
name: Wurtele, Eve Syrkin
name: Corvelo, André
name: Geiger, Heather
name: Craney, Arryn
name: Rendeiro, André F.
name: Wu, Shixiu
name: Salvatore, Mirella
name: Cushing, Melissa
name: Danko, David C.
name: Borczuk, Alain C.
name: Mason, Christopher E.
name: Warren, Sarah
name: Butler, Daniel J.
name: Germer, Soren
name: Levy, Shawn
name: Beheshti, Afshin
name: Saravia-Butler, Amanda
name: Reeves, Jason
name: MacKay, Matthew
name: Hajirasouliha, Iman
name: Kriegel, Alison J.
name: Fennessey, Samantha
name: Schwartz, Robert E.
name: Zody, Michael C.
name: Hether, Tyler
name: Mozsary, Christopher
name: Schisler, Jonathan
name: Rosiene, Joel
name: Bram, Yaron
name: Chandar, Vasuretha
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2022

description: 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.