TY - JOUR T1 - Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps JF - bioRxiv DO - 10.1101/2021.03.08.434433 SP - 2021.03.08.434433 AU - Jiwoon Park AU - Jonathan Foox AU - Tyler Hether AU - David Danko AU - Sarah Warren AU - Youngmi Kim AU - Jason Reeves AU - Daniel J. Butler AU - Christopher Mozsary AU - Joel Rosiene AU - Alon Shaiber AU - Ebrahim Afshinnekoo AU - Matthew MacKay AU - Yaron Bram AU - Vasuretha Chandar AU - Heather Geiger AU - Arryn Craney AU - Priya Velu AU - Ari M. Melnick AU - Iman Hajirasouliha AU - Afshin Beheshti AU - Deanne Taylor AU - Amanda Saravia-Butler AU - Urminder Singh AU - Eve Syrkin Wurtele AU - Jonathan Schisler AU - Samantha Fennessey AU - André Corvelo AU - Michael C. Zody AU - Soren Germer AU - Steven Salvatore AU - Shawn Levy AU - Shixiu Wu AU - Nicholas Tatonetti AU - Sagi Shapira AU - Mirella Salvatore AU - Massimo Loda AU - Lars F. Westblade AU - Melissa Cushing AU - Hanna Rennert AU - Alison J. Kriegel AU - Olivier Elemento AU - Marcin Imielinski AU - Alain C. Borczuk AU - Cem Meydan AU - Robert E. Schwartz AU - Christopher E. Mason Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/09/2021.03.08.434433.abstract N2 - The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.Competing Interest StatementO.E. is scientific advisor and equity holder in Freenome, Owkin, Volastra Therapeutics and OneThree Biotech. R.E.S. is on the scientific advisory board of Miromatrix Inc and is a consultant and speaker for Alnylam Inc. L.S. is a scientific co-founder and paid consultant. C.M is a consultant for Onegevity Health. C.E.M. is a cofounder of Biotia and Onegevity Health. T.H, S.W., Y. K., and J.R. are employees of Nanostring Inc. The remaining authors declare no competing financial interests. ER -