Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.
|
IF: 0
|
Cited by: 8
|

Abstract

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.

Keywords

GeoMx DSP
Spatial Omics
Spatial Transcriptomics
RNAscope
Spatial Gene Expression

Authors

Park, Jiwoon
Foox, Jonathan
Hether, Tyler
Danko, David
Warren, Sarah
Kim, Youngmi
Reeves, Jason
Butler, Daniel J
Mozsary, Christopher
Rosiene, Joel
Shaiber, Alon
Afshinnekoo, Ebrahim
MacKay, Matthew
Bram, Yaron
Chandar, Vasuretha
Geiger, Heather
Craney, Arryn
Velu, Priya
Melnick, Ari M
Hajirasouliha, Iman
Beheshti, Afshin
Taylor, Deanne
Saravia-Butler, Amanda
Singh, Urminder
Wurtele, Eve Syrkin
Schisler, Jonathan
Fennessey, Samantha
Corvelo, André
Zody, Michael C
Germer, Soren
Salvatore, Steven
Levy, Shawn
Wu, Shixiu
Tatonetti, Nicholas
Shapira, Sagi
Salvatore, Mirella
Loda, Massimo
Westblade, Lars F
Cushing, Melissa
Rennert, Hanna
Kriegel, Alison J
Elemento, Olivier
Imielinski, Marcin
Borczuk, Alain C
Meydan, Cem
Schwartz, Robert E
Mason, Christopher E

Recommend literature





Similar data