RT Journal Article
SR Electronic
T1 Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.08.434433
DO 10.1101/2021.03.08.434433
A1 Jiwoon Park
A1 Jonathan Foox
A1 Tyler Hether
A1 David Danko
A1 Sarah Warren
A1 Youngmi Kim
A1 Jason Reeves
A1 Daniel J. Butler
A1 Christopher Mozsary
A1 Joel Rosiene
A1 Alon Shaiber
A1 Ebrahim Afshinnekoo
A1 Matthew MacKay
A1 Yaron Bram
A1 Vasuretha Chandar
A1 Heather Geiger
A1 Arryn Craney
A1 Priya Velu
A1 Ari M. Melnick
A1 Iman Hajirasouliha
A1 Afshin Beheshti
A1 Deanne Taylor
A1 Amanda Saravia-Butler
A1 Urminder Singh
A1 Eve Syrkin Wurtele
A1 Jonathan Schisler
A1 Samantha Fennessey
A1 André Corvelo
A1 Michael C. Zody
A1 Soren Germer
A1 Steven Salvatore
A1 Shawn Levy
A1 Shixiu Wu
A1 Nicholas Tatonetti
A1 Sagi Shapira
A1 Mirella Salvatore
A1 Massimo Loda
A1 Lars F. Westblade
A1 Melissa Cushing
A1 Hanna Rennert
A1 Alison J. Kriegel
A1 Olivier Elemento
A1 Marcin Imielinski
A1 Alain C. Borczuk
A1 Cem Meydan
A1 Robert E. Schwartz
A1 Christopher E. Mason
YR 2021
UL http://biorxiv.org/content/early/2021/03/09/2021.03.08.434433.abstract
AB 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.